Baclofen Pump

Ontario Health Technology Assessment Series 2005; Vol. 5, No.
Intrathecal Baclofen
Pump for Spasticity
An Evidence-Based Analysis
May 2005
Medical Advisory Secretariat

Ministry of Health and Long-Term Care
Suggested Citation
This report should be cited as follows:
Medical Advisory Secretariat. Intrathecal baclofen pump for spasticity: an evidence-based analysis.
Ontario Health Technology Assessment Series 2005; 5(7)
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Contact Information
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Ministry of Health and Long-Term Care
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Intrathecal Baclofen Pump - Ontario Health Technology Assessment Series 2005; Vol. 5, No. 7
2
About the Medical Advisory Secretariat
The Medical Advisory Secretariat is part of the Ontario Ministry of Health and Long-Term Care. The
mandate of the Medical Advisory Secretariat is to provide evidence-based policy advice on the
coordinated uptake of health services and new health technologies in Ontario to the Ministry of Health
and Long-Term Care and to the healthcare system. The aim is to ensure that residents of Ontario have
access to the best available new health technologies that will improve patient outcomes.
The Medical Advisory Secretariat also provides a secretariat function and evidence-based health
technology policy analysis for review by the Ontario Health Technology Advisory Committee (OHTAC).
The Medical Advisory Secretariat conducts systematic reviews of scientific evidence and consultations
with experts in the health care services community to produce the Ontario Health Technology
Assessment Series.
About the Ontario Health Technology Assessment Series
To conduct its comprehensive analyses, the Medical Advisory Secretariat systematically reviews available
scientific literature, collaborates with partners across relevant government branches, and consults with
clinical and other external experts and manufacturers, and solicits any necessary advice to gather
information. The Medical Advisory Secretariat makes every effort to ensure that all relevant research,
nationally and internationally, is included in the systematic literature reviews conducted.
The information gathered is the foundation of the evidence to determine if a technology is effective and
safe for use in a particular clinical population or setting. Information is collected to understand how a
new technology fits within current practice and treatment alternatives. Details of the technology’s
diffusion into current practice and information from practicing medical experts and industry, adds
important information to the review of the provision and delivery of the health technology in Ontario.
Information concerning the health benefits; economic and human resources; and ethical, regulatory,
social and legal issues relating to the technology assist policy makers to make timely and relevant
decisions to maximize patient outcomes.
If you are aware of any current additional evidence to inform an existing Evidence-Based Analysis, please
contact the Medical Advisory Secretariat: MASInfo@moh.gov.on.ca. The public consultation process is
also available to individuals wishing to comment on an analysis prior to publication. For more
information, please visit
http://www.health.gov.on.ca/english/providers/program/ohtac/public_engage_overview.html
Disclaimer
This evidence-based analysis was prepared by the Medical Advisory Secretariat, Ontario Ministry of Health
and Long-Term Care, for the Ontario Health Technology Advisory Committee and developed from
analysis, interpretation and comparison of scientific research and/or technology assessments conducted
by other organizations. It also incorporates, when available, Ontario data, and information provided by
experts and applicants to the Medical Advisory Secretariat to inform the analysis. While every effort has
been made to do so, this document may not fully reflect all scientific research available. Additionally,
other relevant scientific findings may have been reported since completion of the review. This evidence-
based analysis is current to the date of publication. This analysis may be superceded by an updated
publication on the same topic. Please check the Medical Advisory Secretariat Website for a list of all
evidence-based analyses: http://www.health.gov.on.ca/ohtas.
3
Table of Contents
Abbreviations/Acronyms 6
Executive Summary 7
Objective 7
The Technology 7
Review Strategy 8
Summary of Findings 8
Objective 9
Background 9
Clinical Need: Target Population and Condition 9
Existing Treatments Other Than Technology Being Reviewed 11
New Technology Being Reviewed 13
Intrathecal Baclofen Pump 13
Regulatory Status 14
Literature Review on Effectiveness 16
Objective 16
Questions Asked 16
Methods 16
Inclusion criteria 16
Exclusion criteria 16
Interventions 16
Literature Search 16
Outcomes of Interest 16
Results of Literature Review for Intrathecal Baclofen for Spasticity 17

Summary of Existing Health Technology Assessments 17
Summary of Medical Advisory Secretariat Review of Intrathecal Baclofen for Spasticity 43
Economic Analysis 69
Results of Literature Review on Economics of Intrathecal Baclofen Infusion 69
Ontario-Based Economic Analysis 80
Existing Guidelines for Use of Technology 83
Conclusion 86
Appraisal/Policy Development 86
Policy Considerations/Implications 86
Patient Outcomes 86
4
Demographics 87
Stakeholders 87
System pressures 87
Glossary 88
Appendices 89
Appendix 1. Intrathecal Pump. 89
References 90
5
Abbreviations/Acronyms
ABI Acquired brain injury
ADL Activities of daily living
AI Ambulation index
BT Botulinum toxin
CNS Central nervous system
CP Cerebral palsy
CSF Cerebrospinal fluid
EDSS Expanded disability status scale
ES Effect size
FIM Functional independence measure
GMFCS Gross motor function classification system
GMFM Gross motor function measure
HRQoL Health related quality of life
HSCL Hopkins symptom checklist
ISS Incapacity status scale
MS Multiple sclerosis
OT Occupational therapy
QLI Quality of life index
QoL Quality of life
SCI Spinal cord injury
SDR Selective dorsal rhizotomy
SIP Sickness impact profile
6
Executive Summary
Objective
To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of intrathecal baclofen

for spasticity.
The Technology
Spasticity is a motor disorder characterized by tight or stiff muscles that may interfere with voluntary
muscle movements and is a problem for many patients with multiple sclerosis (MS), spinal cord injury
(SCI), cerebral palsy (CP), and acquired brain injury (ABI).(1). Increased tone and spasm reduces
mobility and independence, and interferes with activities of daily living, continence and sleep patterns.
Spasticity may also be associated with significant pain or discomfort (e.g., due to poor fit in braces,
footwear, or wheelchairs), skin breakdown, contractures, sleep disorders and difficulty in transfer.
Goals of treatment are to decrease spasticity in order to improve range of motion, facilitate movement,
reduce energy expenditure and reduce risk of contractures. Existing treatments include physical therapy,
oral medications, injections of phenol or botulinum toxin, or surgical intervention.
Baclofen is the oral drug most frequently prescribed for spasticity in cases of SCI and MS.(1) Baclofen is
a muscle relaxant and antispasticity drug. In the brain, baclofen delivered orally has some supraspinal
activity that may contribute to clinical side effects. The main adverse effects of oral baclofen include
sedation, excessive weakness, dizziness, mental confusion, and somnolence.(2) The incidence of adverse
effects is reported to range from 10% to 75%.(2) Ochs et al. estimated that approximately 25-30% of SCI
and MS patients fail to respond to oral baclofen.(3;4)
Adverse effects appear to be dose-related and may be minimized by initiating treatment at a low dose and
gradually titrating upwards.(2) Adverse effects usually appear at doses >60 mg/day.(2) The rate of
treatment discontinuation due to intolerable adverse effects has generally been reported to range from 4%
to 27%.(2)
When baclofen is administered orally, only a small portion of the original dose crosses the blood brain
barrier and enters the central nervous system (CNS) fluid, which is the site of drug action. In order to
bypass the oral route, baclofen may be administered intrathecally by infusion directly to the CNS.
Candidates for intrathecal baclofen infusion are patients with spasticity who have intractable spasticity
uncontrolled by drug therapy, or who experience intolerable side effects from oral baclofen.
Advantages of intrathecal baclofen infusion are:

 Direct drug administration to the cerebrospinal fluid (CSF)
o The central side effects of oral baclofen, such as drowsiness or confusion, appear to be
minimized with intrathecal administration.
o The intrathecal delivery of baclofen concentrates the drug in the CSF at higher levels than
those attainable via the oral route.
o Intrathecal administration can use concentrations of baclofen of less than one hundredth
of those used orally.(5)
7
 Adjustable/programmable continuous infusion makes it possible to finely titrate patients’ doses and to
vary the doses over the hours of the day. For example, the dose can be relatively low to give the
patients the extensor tone needed for ambulation during the day and increased at night, thereby
improving quality of sleep.
 Reversible (in contrast to surgery).
A patient who is a candidate for intrathecal baclofen infusion must have no contraindications to the
insertion of an intrathecal catheter (e.g., anticoagulant therapy, coagulopathy, local or systemic infection,
anatomical abnormality of the spine).
Review Strategy
The Medical Advisory Secretariat reviewed the literature to assess the effectiveness, safety, and cost-
effectiveness of intrathecal baclofen to treat patients who have intractable spasticity uncontrolled by drug
therapy, or who experience intolerable side effects to oral baclofen.
The Medical Advisory Secretariat used its standard search strategy to retrieve international health
technology assessments and English-language journal articles from selected databases.
Summary of Findings
• Level 2 evidence supports the effectiveness of intrathecal baclofen infusion for the short-term
reduction of severe spasticity in patients who are unresponsive or cannot tolerate oral baclofen
• Level 3 evidence supports the effectiveness of intrathecal baclofen for the long-term reduction of
severe spasticity in patients who are unresponsive or cannot tolerate oral baclofen
• Level 4 qualitative evidence demonstrates functional improvement for patients who are unresponsive
or cannot tolerate oral baclofen
• Intrathecal baclofen is cost-effective with costs which may or may not be avoided in the Ontario
health system
• True functional use remains to be determined
8
Objective
To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of intrathecal baclofen
for spasticity.
Background
Clinical Need: Target Population and Condition
Spasticity is a motor disorder characterized by tight or stiff muscles that may interfere with voluntary
muscle movements and is a problem for many patients with multiple sclerosis (MS), spinal cord injury
(SCI), cerebral palsy (CP), and acquired brain injury (ABI).(1) Increased tone and spasm reduce mobility
and independence and interfere with activities of daily living, continence and sleep patterns. Spasticity
may also be associated with significant pain or discomfort (e.g., due to poor fit in braces, footwear, or
wheelchairs), skin breakdown, contractures, sleep disorders and difficulty in transfers.(1)
Spasticity develops gradually after the initial insult to the central nervous system (CNS). It usually
becomes noticeable in the first few months but the timing can vary depending on the underlying
neurologic insult. Once recovery from the neurologic deficit stabilizes, the spasticity also tends to
stabilize.
Spasticity is not always detrimental. Spasticity provides posture and tone to a limb that can assist with
weight bearing, even if the patient cannot walk. However, excessive tone may also interfere with
activities. Therefore, it is only when spasticity interferes with function or puts the patient at risk of
hurting himself or herself that it needs to be treated.
Spasticity can be aggravated by noxious stimuli that increase the afferent input (incoming nerve message
to the CNS) on the stretch reflex. These stimuli include: urinary tract infections, constipation, ingrown
toenails, pressure ulcers and poor fit in a brace or wheelchair. Such factors should be examined before
initiating treatment.
The estimated incidence of these conditions is shown below:
Multiple Sclerosis
MS is an inflammatory disease that results in myelin loss in the CNS, with secondary axonal loss. This
leads to the development of plaques in the brain and spinal cord. The etiology is unknown, however, it is
hypothesized that MS is the result of an autoimmune response.
The clinical pattern is variable in severity and is unpredictable.(3) People with MS develop a range of
symptoms including fatigue, memory and attention difficulties, bowel and bladder problems, weakness,
pain and increased muscle stiffness (increased tone or spasticity). Approximately one third of MS
patients will require assistance to walk or be dependent within 15 years of diagnosis.(3)
The prevalence of MS in the United Kingdom (UK) is approximately 100 per 100,000. In Canada, the
prevalence of MS is approximately 100-200 per 100,000.
Cerebral Palsy
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CP is a motor disorder appearing before the age of 3 years due to non-progressive damage to the brain.
Cerebral palsy occurs in 2-3/1000 children.(3) CP is a heterogenous condition, but 80-90% of cases will
have spasticity, which usually affects at least one lower limb.(6)
Quadriplegia (loss of movement and sensation in both the arms and legs) accounts for approximately 7%
of CP.
Patients with diplegic CP (loss of movement and sensation in corresponding limbs on both sides of the
body) account for 44% of those with CP, and are usually able to walk with aids.(3) Around the age of 8
years, however, their mobility fails to improve, leading in some cases to wheelchair confinement.(3) This
is due to an increasing mismatch between weight and strength as well as muscle contractures developing
as a result of spasticity. Orthopedic surgery is needed for contractures to elongate the muscle at the
tendons and increasingly all muscles are operated upon together.(3)
Spinal Cord Injury/Acquired Brain Injury
Spinal cord injury occurs as a result of motor vehicle accidents, violence, falls, diving accidents and work
or sports related injuries. Approximately 55% of SCI patients will be affected by paraplegia (loss of
movement and sensation in the lower body) while 44% are affected by quadriplegia (loss of movement
and sensation in both the arms and legs).
Spasticity is reported to develop within one year of injury in 67% of patients; 37% receive antispastic
medication and 11% fail to respond to the treatment.(3;7) Sampson estimated that approximately 5%
to10% of SCI patients will require intrathecal drug delivery systems to treat excessive spasticity.(3)
Acquired brain injury due to hypoxic brain injury or trauma is a further cause of cerebral spasticity.(3)
The proportion of patients who have severe intractable spasticity uncontrolled by drug therapy has not
been reported in the literature. The London Health Sciences Centre Business Plan reported that the
number of treatable patients with spasticity associated with ABI is rare.
Clinical Scoring Systems to Assess Spasticity
Two commonly used and validated clinical scoring systems to assess spasticity include the Ashworth
scale (Table 1) and the spasm frequency or reflex scale (Table 2).(4)
Table 1: Ashworth Scale

Grade Degree of Muscle Tone
1 No increase in tone
2 Slight increase in tone, giving a “catch” when affected part is moved in flexion or extension
3 More marked increase in tone, but affected part easily flexed
4 Considerable increase in tone; passive movement difficult
5 Affected part rigid in flexion or extension
Table reprinted with permission from Harvey Whitney Books; Lewis KS, Mueller WM. Intrathecal baclofen for severe spasticity
secondary to spinal cord injury. Ann Pharmacother 1993; 27:767-774
10
Table 2: Reflex Scale
Score Reflex Response
0 No response
1 Hyporeflexia
2 Normal response
3 Mild hyperreflexia
4 4 beats clonus
5 Unsustained clonus, >4 beats
6 Sustained clonus
Table 2 reprinted with permission from Harvey Whitney Books; Lewis KS, Mueller WM. Intrathecal baclofen for severe
spasticity secondary to spinal cord injury. Ann Pharmacother 1993; 27:767-774
Existing Treatments Other Than Technology Being Reviewed
Goals of Treatment
Decrease spasticity to improve range of motion
Decrease pain
Facilitate movement
Reduce energy expenditure
Reduce risk of contractures
Physical Therapy
Patients and caregivers are taught to avoid certain postures and noxious or external stimuli that promote
or exacerbate spasticity.(1) Regular stretching is important to prevent contractures and to maintain the
range of movement. Braces may be used to maintain a spastic limb in a reflex-inhibiting posture and
prevent contractures.(1)
Oral Medications
Randomized controlled trials (RCTs) have reported antispasticity medications to be efficacious in the
management of spasticity, especially in adults with spinal disorders (e.g., SCI and MS).(1) Their efficacy
in cerebral disorders (ABI, stroke, CP) is less studied in adults and especially in children. The
medications commonly used are baclofen, dantrolene, tizanidine, gabapentin, and benzodiazepines.(1;3)
Many antispasticity oral drug trials have been conducted in adults with spastic disorders, with relatively
few trials done in children.(8;9)
In 2004 Montane et al. conducted a systematic review of oral antispastic drugs in nonprogressive
neurologic diseases.(10) Twelve randomized controlled trials (RCTs) (N=469 patients) were included (6
on stroke, 3 on spinal cord diseases, and 3 on CP). The patients with CP were all children (n=67).
Tizanidine was assessed in 4 trials (276 patients, 142 exposed), dantrolene in 4 (103 patients, 93
exposed), baclofen in 3 trials (70 patients, 55 exposed), diazepam in 2 trials (127 patients, 76 exposed),
and gabapentin in one trial (28 patients, all exposed).(10) Only one trial investigating the use of oral
baclofen in children (N=20) with CP was identified.(11)
Most of the trials had small sample sizes, and were of short duration with inadequate methodologic
quality.(10) Sample size calculations were not reported in any trial. Ten trials were controlled with
placebo and 2 were direct comparisons between drugs. Efficacy outcomes of interest were variable
among the studies. Four trials described the magnitude of the antispastic effect. Adverse effects were
generally more frequent in the active treatment groups (range 25% to 91%) than in the placebo groups
(range 0% to 53%). Baclofen was associated with sedation, dizziness and muscle weakness (range of
adverse events of 25 to 27% of patients).(10)
11
Montane et al. concluded that the evidence on the efficacy of oral antispastic drugs in nonprogressive
neurologic diseases is weak, and does not include evaluation of patients’ quality of life (QoL).(10)
Baclofen is the oral drug most frequently prescribed for spasticity in cases of SCI and MS.(1) Baclofen is
a muscle relaxant and antispasticity drug that is a structural analogue of the inhibitory neurotransmitter
gamma-aminobutyric acid (GABA). Baclofen binds to presynaptic GABA-B receptors within the brain
stem, dorsal horn of the spinal cord and other CNS sites. In the brain, baclofen delivered orally has some
supraspinal activity that may contribute to clinical side effects. The main adverse effects of oral baclofen
include sedation, excessive weakness, dizziness, mental confusion, and somnolence.(2) The incidence of
adverse effects is reported to range from 10% to 75%.(2) Ochs et al. estimated that approximately 25%-
30% of SCI and MS patients fail to respond to oral baclofen.(3;4)
Adverse effects appear to be dose-related and may be minimized by initiating treatment at a low dose and
gradually titrating upwards.(2) Adverse effects usually appear at doses >60 mg/day.(2) The rate of
treatment discontinuation due to intolerable adverse effects has generally been reported to range from 4%
to 27%.(2)
When baclofen is administered orally, only a small portion of the original dose crosses the blood brain
barrier and enters the CNS fluid, which is the site of drug action. In order to bypass the oral route,
baclofen may be administered intrathecally by infusion directly to CNS.
Injections of Phenol or Botulinum Toxin

Focal treatment of spastic muscles has been used in people with cerebral spasticity.(1) The goal is to
block the final common nerve pathway. Phenol injections have been used to block large nerves going to
specific regions of the body that are spastic.(1) Complications of phenol injections that have been
reported include pain, peripheral edema, skin sloughing and wound infection.(1)
Botulinum toxin type A injections have been used to block the neuromuscular junction with resultant
weakness (reduction of muscle tone).(1) There is a maximal total dose according to body weight for each
course of treatment, beyond which the toxin escapes into the systemic circulation in significant amounts
to cause general fatigue. Due to the limited amount that can be given safely at one time, only a small
number of muscles can be treated every 4-6 months. Limited muscle pain, bruising and transient fever
may occur on the day of the injection.
The major indications for botulinum toxin include the relief of spasticity in the calves in children with
hemiplegic CP (loss of movement and sensation in the right or left half of the body) and the calves,
hamstrings and hip adductors in diplegics.(3) Botulinum can also be used in patients with quadriplegia,
particularly in the hip adductors. However, it is not usually considered for SCI patients since the treatment
is not appropriate in generalized spasticity.
Surgical Intervention
Due to the invasiveness of the procedure, surgical treatment of spasticity is reserved for the most
refractory cases.(1)
Selective dorsal rhizotomy (SDR) of the lumbrosacral nerves is a neurosurgical procedure designed by
Fasano et al. in 1978 to treat spasticity in the lower extremities of children with CP.(12) The surgery
requires testing individual sensory nerve rootlets to determine those rootlets that when stimulated,
produce abnormal electrophysiologic responses. Rootlets producing abnormal responses are cut and
normal responding rootlets are spared.
12
Other surgical procedures include myelotomy (incision of the spinal cord) and cordotomy or cordectomy
(excision of part of the cord).(1) Many orthopedic procedures such as lengthening, releasing or
transferring a tendon, may be helpful in optimizing function and preventing contractures.(1) Osteotomies
(cutting of bone) may be undertaken to correct deformity.
New Technology Being Reviewed

Intrathecal Baclofen Pump
Candidates for intrathecal baclofen infusion are patients with spasticity who have intractable spasticity
uncontrolled by drug therapy or who experience intolerable side effects to oral baclofen.
Test Procedure
Before implantation, a bolus dose of baclofen is injected into the CSF using a lumbar puncture or a
temporary catheter, under local anesthesia, to screen for a patient response to treatment. The dose of
baclofen is titrated upwards in 25 microgram per day aliquots until an approximately 4 to 8 hour response
is observed. If the patient does not respond to 100 micrograms intrathecally, the patient is considered to
have an inadequate response and should not undergo implantation.
Creedon et al. stated that generally, patients considered as candidates for pump implantation are those that
have decreased spasticity, as indicated by a 2 point or more decrease in their Ashworth or Penn spasm
scale scores, for a period of 4-8 hours after the bolus injection.(13) Some patients do not have any
response; others do not respond substantially enough to justify implantation. A few patients who have
adequate reduction in spasticity from intrathecal administration decline implantation because muscle tone
they used for functional activities was lower during the trial than prior to trial.(13)
Pump Implantation
An intrathecal pump delivers baclofen directly into the CSF. The system consists of a catheter and a
pump (Appendix 1). The pump is surgically placed under the skin of the abdomen near the waistline,
under general anesthesia. The pump stores and releases prescribed amounts of medication through the
catheter. The pump is refilled by inserting a needle through the skin into a filling port in the centre of the
pump.
Pumps can be programmable or nonprogrammable. Using an external programmer, a physician can make
adjustments in the dose, rate and timing. The pump reservoir can be refilled approximately every 2-3
months by percutaneous injection. The pump is taken out and replaced at the end of the battery’s life
span (approximately 5-7 years).
Length of Treatment
The length of time that the treatment will be administered depends upon the nature of the underlying
disease. For a progressive disease (e.g., MS), the length of time intrathecal baclofen infusion may be
beneficial will be dependent upon the progression of the disease. For other conditions such as SCI or CP,
where progression does not affect the spasticity, there is no defined limit as to how long the treatment
may be required and there are no firm recommendations for tolerance management. Drug holidays have
been reported as an approach to the management of tolerance. (13)
13
Due to limited battery life, the initial pump procedure will need to be repeated every 5-7 years. The
dosage of baclofen may be increased due to increased tolerance of the drug.
Advantages of intrathecal baclofen infusion are:

 Direct drug administration to the CSF:
o The central side effects of oral baclofen such as drowsiness or confusion appear to be
minimized with intrathecal administration.
o The intrathecal delivery of baclofen concentrates the drug in the CSF at higher levels than
those attainable via the oral route.
o Intrathecal administration can use concentrations of baclofen of less than one hundredth
of those used orally.(5)
 Adjustable/programmable continuous infusion makes it possible to finely titrate patients’ doses and to
vary the doses over the hours of the day. For example, the dose can be relatively low to give the
patients the extensor tone needed for ambulation during the day, and increased at night, thereby
improving quality of sleep.
 Reversible (in contrast to surgery).
A patient who is a candidate for intrathecal baclofen infusion must have no contraindications to the
insertion of an intrathecal catheter (e.g., anticoagulant therapy, coagulopathy, local or systemic infection,
anatomical abnormality of the spine).
Sampson et al.(3) reported the estimated incidence and prevalence of spasticity in conditions potentially
amenable to treatment with intrathecal baclofen infusion. Assuming an Ontario population of 12 million,
the following prevalent and incident cases in Ontario are estimated in Table 3.
The estimated prevalence and incidence of SCI, CP and MS from the literature is shown in Table 3.
Table 3: Estimated prevalence and incidence of SCI, CP and MS from the literature
Condition Incidence per Prevalence per
100,000 per year 100,000
SCI 1.7 72
CP 2.6 50
MS 3-7 100-200
According to Sampson et al., in 1998, approximately 200 patients in Britain were implanted with pumps
for intrathecal baclofen.(3) Approximately 60% were SCI patients, 30% had MS and the remaining 10%
of patients had an underlying cause of spasticity due to other causes such as CP, traumatic brain injury
and metabolic disorders.(3)
Regulatory Status
The following products are licensed by Health Canada as Class 3 devices for intrathecal baclofen
infusion:
 Synchromed EL System®, Synchromed System®, Medtronic Inc. (License # 7444, and 934
respectively).
 Constant Flow M3000 Series Implantable Infusion Pump®, Codman & Shurtleff Inc. (License #
12699).
14
 Infusaid Constant Flow Implantable Infusion Pump, Codman & Shurtleff Inc. (License # 14493).
 Archimedes Implantable Infusion Pump®, Codman Neuro Sciences Sarl, A Johnson & Johnson
Company, (License # 61965).
According to the 2005 Compendium of Pharmaceuticals and Specialties, the indications for intrathecal
baclofen are:
“For the management of patients with severe spasticity due to spinal cord injury or multiple
sclerosis who are unresponsive to oral baclofen or who experience unacceptable side effects at
effective oral doses.”(14)
In July 2002, Health Canada posted drug safety information regarding Lioresal intrathecal (baclofen).(15)
The notice provided updated information to include warnings about rate cases of intrathecal baclofen
withdrawal that can lead to life-threatening sequelae and/or death in patients who abruptly discontinue
therapy.(15)
At the time of the Health Canada posting, Lioresal Intrathecal was indicated for the management of patients
with severe spasticity due to spinal cord injury or multiple sclerosis who are unresponsive to oral baclofen or
who experience unacceptable side effects at effective oral doses.(15)
The following box warning was added to the Lioresal intrathecal product monograph:
“Abrupt discontinuation of intrathecal baclofen, regardless of the cause, has resulted in sequelae
that include high fever, altered mental status, exaggerated rebound spasticity, and muscle
rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure and
death.
Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to proper

programming and monitoring of the infusion system, refill scheduling and procedures, and pump
alarms. Patients and caregivers should be advised of the importance of keeping scheduled refill
visits and should be educated on the early symptoms of baclofen withdrawal. Special attention
should be given to patients at apparent risk (e.g. spinal cord injuries at T-6 or above,
communication difficulties, history of withdrawal symptoms from oral or intrathecal baclofen).
Consult the technical manual of the implantable infusion system for additional postimplant
clinician and patient information. (see WARNINGS).”(15)
Lioresal® Intrathecal was approved for the treatment of cerebral spasticity by the United States Food and
Drug Administration (FDA) in June 1996. Children must be at least 4 years of age and large enough to
accommodate the implanted pump. Prior to 1996, intrathecal baclofen was FDA-approved for spasticity
due to SCI and MS.
15
Literature Review on Effectiveness
Objective
The Medical Advisory Secretariat did a literature review to assess the effectiveness, safety, and cost-
effectiveness of intrathecal baclofen to treat spasticity.
Questions Asked
 Does intrathecal baclofen improve gait, activities of daily living and hygiene?
 Does intrathecal baclofen decrease spasm frequency?
 Does intrathecal baclofen defer time to orthopedic surgery?
Methods
Inclusion criteria
English-language articles (April 2003 – 2004)
Journal articles that reported primary data on the effectiveness or cost-effectiveness of data obtained in a
clinical setting, or analysis of primary data maintained in registries or databases
Study design and methods that were clearly described
Systematic reviews, randomized controlled trials (RCTs), non-RCTS or cohort studies that had >20
patients, and cost-effectiveness studies
Exclusion criteria
Duplicate publications (superseded by another publication by the same investigator group, with the same
objective and dataNon-English-Language articles
Non-systematic reviews, letters and editorials
Animal and in-vitro studies
Case reports
Studies that did not examine the outcomes of interest
Interventions
Intrathecal baclofen infusion
Controls underwent optimal conventional management
Literature Search
Cochrane database of systematic reviews
ACP Journal Club
DARE
INAHTA
EMBASE
MEDLINE
Reference sections from reviews and extracted articles
Outcomes of Interest
Reduction of spasticity
Activities of daily living
16
QoL
Adverse effects
Economic analysis data
Results of Literature Review for Intrathecal Baclofen for Spasticity
Summary of Existing Health Technology Assessments
Six international health technology assessments were identified in the literature search. The most recent
assessment was conducted by the Australian Safety and Efficacy Register of New Interventional
Procedures-Surgical (ASERNIP-S) in May 2003. ASERNIP-S did not report finding a previously
conducted meta-analysis from 1997 by Creedon et al.(13) in their literature search (reason not stated).
ASERNIP-S also stated that the systematic review by Taricco et al.(16) (discussed later in this document)
was not included in their analysis (reason not stated).
Another HTA by Sampson et al.(3) from the Trent Institute for Health Services Research published in
2000, and fully discussed later in this document, reported on and analyzed the meta-analysis by Creedon
et al.(13) A review and commentary of the meta-analysis by Creedon et al. from the Trent Institute for
Health Services Research report is provided below.
Foundation of Most International HTAs: Meta-analysis of Intrathecal Baclofen (Creedon

et al., 1997)(13)
Creedon et al. (13) conducted a meta-analysis of English-language trials of intrathecal baclofen infusion
that were published prior to June 1996. In total, 27 studies were included (N=490 patients; n=206 SCI
patients; n=162 MS patients; n=59 CP patients; n=64 patients with other causes of spasticity). Patients
had spasticity resistant to oral medication. The average patient in the meta-analysis was 36 years old, 7
years post-onset of the CNS disorder, and had undergone followup evaluations for 18 months after
implantation of the pump.(3)
Overall results indicated that:

 91% of patients who were screened had a positive response to screening
 92% of patients who had a pump implanted had a positive response to the pump;
 92% of patients who had a pump implanted were still using the pump at one-year followup.
The overall effect on the Ashworth and spasm scores, and the effect in different patient groups is shown
in Table 4.
17
Table 4: Effect of intrathecal baclofen on Ashworth and spasm
Condition Mean Mean N* P value Mean Mean Spasm N* P value
Ashworth Ashworth Spasm Score post
Score pre Score post Score pre intrathecal
intrathecal intrathecal intrathecal baclofen
baclofen baclofen baclofen
All patients 3.9 1.6 134 <0.001 3.2 0.6 51 <0.001
MS 4.2 1.3 43 <0.001 3.2 0.4 18 <0.001
CP 2.9 2.0 23 0.34 - - 0 -
SCI 4.0 1.7 49 <0.001 3.4 0.8 21 <0.001
Other 4.3 1.7 19 <0.001 3.2 0.8 11 <0.001
*Number of patients on which estimate is based.
Table reprinted with permission; From Sampson FC, Hayward A, Evans G, Touch S, Morton R, Vloeburghs M et al. The
effectiveness of intrathecal baclofen in the management of patients with severe spasticity. 2000. Sheffield: Trent Institute for
Health Services Research, Universities of Leicester, Nottingham and Sheffield. Guidance Note for Purchasers: 00/01
The effect on spasticity in CP patients was less marked than in other patients possibly because the meta-
analysis did not include many patients with CP, and these patients had less severe spasticity at baseline
than other patients.
The dosage of baclofen required to achieve spasticity reduction increased during followup. The average
starting dose was around 150 micrograms per day and after 16 months, this increased by approximately
250%.(3)
Summary of International Health Technology Assessments
Australian Safety and Efficacy Register of New Interventional Procedures-Surgical

(ASERNIP-S), Australia, 2003
A detailed summary of the 2003 ASERNIP-S report is provided below.
A literature search was conducted up to April 2003. In total, 53 studies of intrathecal baclofen infusion
were identified. Seven RCTs were excluded from the analysis because “they were internal comparisons
assessing the efficacy of intrathecal baclofen (for spasticity or dystonia) to intrathecal saline (studies were
usually of double blind, crossover design, followed with an observational study of intrathecal
baclofen).”(17) Forty-four case series/case reports were also excluded. In the end, 2 case series studies
were included “with regard to patient numbers and length of followup to present a snapshot of safety and
efficacy”.
Study characteristics of these 2 case series are presented in Table 5.
18
Table 5: Characteristics of case series studies included in ASERNIP-S assessment
Author Intervention Study Design Study Population Inclusion/Exclusion
Criteria
Ordia et al., 2002 Screening Trial Case Series Sample Size: Inclusion Criteria:
USA Bolus injection of intrathecal 131 patients (152 patients screened) Patients interviewed and
baclofen given by lumbar Followup: examined to determine
puncture or via intrathecal Mean 73 months (range Age: suitability.
catheter 2-137) Mean 42 years (range 17-73) Eligible if patients had a
A double-blind randomized mean Ashworth Score of at
placebo controlled trial was Loss to Followup: Intractable spasticity of spinal cord origin: least 3 and a Spasm
performed on the first 9 Not specifically stated 63/131 (48%) spinal and supraspinal Frequency Score of at least 2
patients; placebo (saline) and but 8/131 (6%) pumps multiple sclerosis in the affected limb.
50ug baclofen were randomly were explanted as 53/131 (40%) spinal cord injury
given on day 1 and day 2. If patients withdrew from 15/131 (12%) other including: Exclusion Criteria:
there was no response to the intrathecal therapy. familial spastic paraparesis Pregnant or of childbearing
baclofen, placebo and 75 ug of lateral sclerosis potential and were not using
baclofen were given on days 3 Study Period: cervical spondylotic myelopathy birth control, patients with a
and 4. Nonresponders were Not stated spinal cord tumour history of allergy to baclofen,
randomized to placebo and 100 transverse myelitis patients with severely
ug baclofen on days 5 and 6.) syringomyelia impaired renal or hepatic
A reduction in the mean spinal epidural abscess function.
Ashworth Score or the mean spinocerebellar degeneration
Spasm Frequency Score for at adrenal leukodystrophy
least 4 hours was considered to
b a positive response. 90/131 (69%) quadriplegic
57 patients were enrolled into 41/131 (31%) paraplegic
an open label treatment protocol
without placebo. 109/131 (83%) nonambulatory
The final 86 patients were 22/131 (17%) ambulatory
treated following FDA approval,
also screened without placebo. Mean duration of symptoms 14 years (5
months-34 years)
Pump
Synchromed Infusion System. Prior medication use
Investigators left an interval of Average daily dose of oral baclofen, 106
several days between screening mg. For patients on diazepam and
and implantation to allow the tizanidine, average daily doses of baclofen
dura to heal and potentially to were 26 mg and 21 mg.
reduce the risk of infection).
Outcome measures and validity:
Ashworth Scale: 1 to 5 (“no increase in
tone” to “affected part(s) rigid in flexion or
extension”)
Spasm Frequency Score:
19
0 to 4 (“none” to “greater than 10
spontaneous spasms per hour”)
Spasticity considered severe if Ashworth

Score was >3 or the Spasm Frequency
Score ws >2.
Stampien and Tsai, Screening Trial Case series Sample Size Inclusion Criteria
2000 Screened by test dose via Clinical survey of 115 centres. Centres currently providing
USA lumbar puncture with the Followup: 40/115 (35%) returned the survey intrathecal baclofen pumps
majority performed with 50ug Not stated 936 pumps had been placed and 1002 test
boluses. 853/978 (87%) doses completed. Exclusion Criteria
reported test doses were Loss to followup Not stated
successful. Not applicable – survey Age
of centres Not stated
Pump
SynchroMed. 936 pumps Study Period Spasticity
placed. Summer 1998, clinical Spasticity reported for 770 patients
survey 336/770 (44%) cerebral palsy
168/770 (22%) spinal cord injury
Operator Details 21/770 (3%) anoxic encephalopathy
17 children’s hospitals 73/770 (9%) traumatic brain injury
15 general hospitals 6/770 (1%) stroke
7 rehabilitation hospitals 166/770 (21%) “other”
1 outpatient facility
Baseline medication use
Not stated
Outcome measures and validity

Not stated
Table reproduced with permission of ASERNIP-S; From Simpson B, Middleton P, Maddern G. Implantable spinal infusion devices for chronic pain and spasticity: an accelerated
systematic review. 2003. Australian Safety and Efficacy Register of New Interventional Procedures - Surgical (ASERNIP-S).
20
Safety results from the 2 case series are shown in Table 6.
Table 6: Safety results from case series in the assessment by ASERNIP-S

Complications Ordia et al. 2002 Stempien and Tsai, 2000
N=152 N=936
Mortality 10/131 (8%) Not attributable to -
CIBI
Drug Related
Constipation 12/131 (9%) patients with 2.9% following implantation
preexisting constipation but
required a more intense bowel
regimen after surgery
Hypotension and bradycardia 2/131 (2%) 12/978 (1%) screening dose - hypotension
0.9% following implantation – hypotension
Muscular hypotonia 7/131 (5%) -
Nausea, vomiting, dizziness, 1/131 (0.8%) nausea, dizziness, 26/978 (3%) screening dose – nausea,
drowsiness/lethargy/fatigue drowsiness vomiting
Sedation - 22/978 (2%) screening dose
Seizures - 3/978 (0.3%) screening dose
1/936 (0.1%) after initial hospitalization
Tolerance 2/131 (1.5%) -
Patients weaned and kept off
baclofen for a 4-6 week drug
holiday but received intrathecal
morphine. When baclofen was
restarted, the effective dose was
less than half of which the
patients were tolerant to and
patients stayed on low dose for
3-4 months before an increase
was needed.
Urinary 4/131 (3%) 16/978 (1.5%) screening dose – 1 case of
retention/hesitancy/disturbances retention
Following implantation – 2 cases retention
Pump Related
Flipped pump 2/131 (1.5%) 1 case following implantation
Stuck valve 1/131 (0.8%) -
Replacement/revision/repositioning - At the time of survey 66/936 (77%) pumps
had been replaced. Reasons were:
16/936 (1.7%) infection
12/936 (1%) battery failure
11/936 (1%) patient request
8/936 (0.9%) hypermobility with effusion
4/936 (0.4%) pump failure
2/936 (0.2%) CSF leak
1/936 (0.1%) dehiscence
1/936 (0.1%) smaller pump placed
11/936 (1%) not stated
Explantation 8/131 (6%) patients withdrew
from therapy
Catheter related 24 catheter related problems in
19 patients. All but 2 occurred
with earlier models of the
catheter
Breaks 8/131 (6%) -
Dislodgement 2/131 (1.5%) -
Occlusion/obstruction/kink 12/131 (9%) -
Punctures 2/131 (1.5%) -
Replacement/revision/repositioning - At the time of survey: 64/936 (7%) catheters
21
had been replaced. Reasons were:
40/936 (4%) kinks or migration
3/936 (0.3%) infection
1/936 (0.1%) occlusion
1/936 (0.1%) arachnoiditis
19/936 (2%) not stated
Wound problems
Pocket erosion 2/131 (1.5%)
Pocket infection 1/131 (0.8%) superficial
Other
CSF leak/collection 1/131 (0.8%) 2.2% following implantation – leak
treated with laminectomy and 3.3% following implantation – collection
dural repair 8/936 (0.9%) after initial hospitalization –
collection
Hematoma 0.8% following implantation
Hydrocephalus 1 case following implantation
Infection 1.5% following implantation
Meningitis 1/131 (0.8%) bacterial meningitis
developed one week after
occluded catheter replaced.
Entire hardware removed and
patients treated with intravenous
antibiotics.
Spinal type/subdural puncture
headache
Following screening trials 10/152 (7%) <1% was stated in text as “headache”
Following implantation 6/131 (5%) 2.4% was stated in text as “headache”
2/6 did not resolve with bed rest
and were treated with autologous
epidural blood patch
Worsened gait - 1 case following implantation
Table reproduced with permission of ASERNIP-S; From Simpson B, Middleton P, Maddern G. Implantable spinal infusion
devices for chronic pain and spasticity: an accelerated systematic review. 2003. Australian Safety and Efficacy Register of New
Interventional Procedures - Surgical (ASERNIP-S).
Efficacy results from the 2 case series are shown in Table 7.
Table 7: Efficacy results from the 2 case series studies

Efficacy Endpoint Ordia et al. 2002 Stempien and Tsai, 2000
N=152 N=936
Ambulatory ability 2/109 (2%) who were -
nonambulatory were able to walk.
Ashworth Score Decrease, mean 4.2 to 1.3 -
(p<0.0005)
Dose escalation Average daily dose was 134 ug After 6 months:
which increased to 247 ug at 6 Lowest daily dose was 25 ug/day
months and 277 ug at 12 months. Highest daily dose was 1500 ug/day
(Dose was stable for spinal cord
injury patients at 12 months but
continued to escalate in multiple
sclerosis patients, probably due to
progression of the disease).
Driving ability 4/131 (3%) could drive (not able to
drive before using the pump)
Gait and balance Improved for 18/22 (82%)
ambulatory patients
Length of stay after implantation Average 2-3 days
Spasm frequency score Mean pre pump 3.4 to post pump
22
0.6
Urodynamic parameters 8 patients had reduced detrusor
hyperreflexia and a bladder
sphincter dyssynergy and increased
bladder capacity.
Some patients (n=?) converted from
an indwelling catheter to intermittent
drainage, and others (n=?) required
fewer daily catheterizations.
Work status Control of spasticity allowed a
number of patients (n=?) to work or
take less sick time.
Miscellaneous comments >90% of centres reported improvements in
areas of daily care
97% reported easier diapering
95% improved transfers
95% improved sitting tolerance
94% easier dressing
94% improved orthotic wear
90% improved dexterity
85% improved contractures
81% improved respiratory function
74% improved ambulation endurance
57% better swallowing function; 1% worse
50% better for drooling, 23% worse
57% better head control, 23% worse
68% better bladder control, 0.5% worse
40% better bowel control, 27% worse
Table reproduced with permission of ASERNIP-S; From Simpson B, Middleton P, Maddern G. Implantable spinal infusion
devices for chronic pain and spasticity: an accelerated systematic review. 2003. Australian Safety and Efficacy Register of New
Interventional Procedures - Surgical (ASERNIP-S).
ASERNIP-S (17) concluded:
“Infusion of baclofen for treatment of spasticity intrathecally via implantable infusion devices
appears effective for patients who have been screened for response to intrathecal medication
prior to implantation. This method of treating spasticity appears safe, although drug related
complications do occur (similar with systemic or parenteral drugs) but device related
complications (such as catheter related complications) can also occur which may result in
surgical revision or removal of the device. Treatment of spasticity via intrathecal baclofen may
be less costly than medical management in the long term.”
National Health Service Research & Development (NHS R&D) United Kingdom, 2003
Beard et al.(18) addressed 2 general questions for NHS R&D:
 What are the treatments currently available for the management of spasticity and pain in MS?
 What is the clinical and cost-effectiveness of each of these treatments for spasticity and pain in MS?
NHS R&D stated that the purpose of the report was to provide a wider perspective of the needs and
potential interventions in MS. It was not possible to cover each individual treatment in great depth. The
report did not look at treatments other than drug therapy.
A literature search was conducted up to July 2000. It was reported that searches were repeated in March
23
2002.
Quantity of Research
Twenty studies evaluating the use of intrathecal baclofen were identified. Five were excluded because the
number of patients with MS was less than 50% of the total; the results for this group of patients were not
presented separately. Fifteen studies were included in the review. Four studies came from the same
centre and it was not clear to what extent the patients were included in more than one of them.
One study was a double-blind RCT lasting 13 weeks.(19) Another was a short-term (3 days) crossover
RCT conducted in 1989.(20) In 1993, Coffey et al. used a double-blind randomized technique in the
initial screening to assess initial response to a bolus dose before recruiting subjects into the open-label
uncontrolled studies.(21) The remaining 12 studies were longitudinal, open label, uncontrolled designs or
case series.
Beard et al. (18) stated that it is unfortunate but understandable given the complex nature of the
intervention that there was only one longer term double-blind RCT.(18) However, researchers may be
either unable or unwilling to randomize or blind patients.(18) Use of a double-blind RCT is unlikely for
this treatment in patients with MS because of the invasive nature of the intervention, possible ethical
issues, the need to titrate dosage over time and the large number of treatment-related complications.
Despite the potential for bias arising from the uncontrolled studies, Beard et al. included them because of
the lack of other evidence. The duration of treatment in the studies ranged from 4 months to 6 years.
Populations Examined
None of the studies were restricted to patients with MS. However, in all included studies, >50% of the
patients had MS or the results for the MS patients were shown separately. In all 15 studies, all patients
had severe spasticity and in 6 studies the patients were stated explicitly to be unresponsive to oral therapy.
In most of the studies, the patients were nonambulatory and most had had their condition for a long time.
Intervention
All studies examined the effect of baclofen administered intrathecally by a programmable continuous
infusion pump. Most of the studies used an initial screening stage in which baclofen was administered as
a bolus dose to test the responsiveness of the patient. If this was successful, a pump and catheter were
then inserted from the administration of baclofen on a long-term basis. The long-term dosage used in
these selected studies ranged from 21 to 648 ug per day.
Outcomes Measured
Several different outcome measures were used. The main ones were the Ashworth scale and various
spasm frequency scales.
Validity of Studies
The longitudinal studies and case series relied on the observation of the patient’s condition prior to
implantation of the pumps as controls against which to assess the impact of the intervention. However,
this does not allow for any change in the condition of the patients that could have occurred spontaneously.
Although MS can be a relapsing and remitting disease, it appears that in the majority of these cases, the
disease was stable.
The sample size of the 11 longitudinal or case series studies ranged from 6 to 93, with many at the lower
end of the range. Some of the studies may not have had adequate levels of statistical power and most did
not attempt to justify their sample size.
Generally there was an absence of data analysis using statistics in the included studies, with many of the
24
studies resorting to qualitative analysis.
Effect on Spasticity (Table 8)

The studies showed an overall positive outcome for patients treated with intrathecal baclofen. All 15
studies reported positive findings. In studies that reported the Ashworth scale, scores fell almost
universally by 2-3 points typically from 3-4 pre-implantation to 1 after treatment. Similarly, there was a
near universal abolition of spasms, which was reflected in spasm frequency scores.
25
Table 8: Summary of studies included in the systematic review by Beard et al.(18)
Study Design Dose Patients Results
Saltuari et al. 1992 Prospective Mean final dose for N=11, of whom 6 had MS Results in MS patients not reported separately.
Austria longitudinal MS patients 239 Age 30-57years Mean Ashworth score:
uncontrolled ug/day. Disease duration 6-27 years For knee flexion reduced from 3.4 to 1.25
Treatment duration For knee extension from 3.4 to 1.4
2-24 months
Patellar reflex score reduced from ~3.9 to ~1.4 (reflex
assessed on a 6 point scale).
One MS patient reported to be able to use staircase.
4 catheter dislocations, one catheter break, one catheter

torsion.
Becker et al. 1995 Prospective Mean dose at N=9, of whom 6 had MS Nursing Assessment: Major improvements in transfers
Canada longitudinal followup for MS Age 34-56 years (5/6), pain control (4/6), nursing care (5/6) and skin
uncontrolled patients 542 ug/day All were nonambulatory and many breakdown (5/6).
Treatment duration could not sit properly owing to
13-34 months their severe spasticity. The MS Self-reported satisfaction survey of MS patients (1-5 score):
patients were all severely disabled All items showed major improvements in particular the
with little or no leg function and ability to transfer, seating ability, personal hygiene, sleeping
marked arm weakness. ability and pain control.
6/9 were unable to live at home.
Average duration of MS 16.5 Place of residence: 3/6 MS patients who were previously
years. hospitalized were able to be discharged.
# days in hospital: Average time spent in hospital reduced

from 108 to 28 days per year.
A number of complications including: surgical catheter

revisions, pseudomeningocele repair and problems with
pump refills.
Broggi et al. 1993 Prospective Mean dose in MS N=12, of whom 4 had MS. Mean score before treatment was 3.8. This feel to 1.8 after
Italy longitudinal patients 178 ug/day. Mean age 50 years. treatment.
uncontrolled Mean duration of Mean duration of disease 16
treatment 9 months years. Muscle spasms were abolished.
Unresponsive to oral therapy.
Mean Ashworth score 3.8. No reported side effects in MS patients. There were pump
All MS patients were bedridden. related complications in other patients.
Penn et al. 1989 Double-blind 100-150 ug/day or N=20, of whom 10 had MS. In MS patients:
USA Crossover saline Ages 31-62 years. No explicit results given for the short-term crossover trial,
RCT administered for 3 One MS patient able to walk a but period of baclofen infusion said to have been correctly
days in short distance with crutches, the identified by each assessment.
randomized rest wheelchair bound.
26
crossover trial. Mean Ashworth score 4.0. In long-term followup, mean Ashworth score decreased
Long term from 4.01 to 1.05; mean spasm score decreased from 2.9 to
followup for mean 0.2.
of 19 months
(mean dose 223 Of 20 patients, in 26 months followup, 2 catheters
ug/day). dislodged, one pump failure, one painful implant site.
Parke et al. 1989 Long term 67-550 ug/day N=8, of whom 4 had MS. May be Ashworth score reduced from 4 or 5 to 1 in all 4 MS
USA followup 3 and 6 months same patients as included in other patients.
followup studies from the same centre.
Bladder care score improved in all 4 patients (indwelling
urinary catheter removed in 1 patient), dressing skills
improved in 2 of 4 patients.
Penn (1992) Case series Mean initial dose N=66, of whom 33 had MS. For all patients:
USA 200 ug/day Presumably some of the same Ashworth score: pre-implantation mean score ~3.7 falling to
patients as included in other ~1.4 after implantation, maintained for up to 81 months.
studies from the same centre. Spasm scale (0-4): pre-implantation mean score ~2.9
falling to 0.8 after implantation, maintained for up to 81
months.
Complications: 1 meningitis, 1 pocket infection, 19 fungal
infection of pumps (no clinical impact, all replaced), 9 pump
failures out of 91 pumps, 25 catheter complications
(various), 5 procedural complications.
Complications of baclofen: drowsiness (n=22), dizziness
(n=10), blurred vision (n=10), slurred speech (n=6).
Broseta et al., 1989 Prospective 60-172 ug/day. N=8, of whom 4 had MS. All patients showed a reduction of at least one point on the
Spain longitudinal Mean followup 5 Age 27-54 years. Ashworth scale.
uncontrolled months. All had severe spasticity and were
unresponsive to oral treatments. All patients showed a reduction in frequency of spasms.
Ashworth score 2-4. 4 cases were
either in a wheelchair or All 4 cases had increased walking ability, transfers and daily
bedbound. activity. The nonambulatory patients gained only in QoL
and comfort.
Coffey et al., 1993 Screening Mean starting dose N=93 patients screened, of whom Ashworth score: mean score decreased from 2.9 to 1.6.
USA protocol was a 171 ug/day. 31 had MS.
double-blind Mean dose at 75 patients had a pump implanted, Frequency of spasm score (0-5): mean score reduced from
RCT, followed followup 320 of whom 27 had MS. 2.7 to 0.7.
by open label ug/day. Average age 42 years.
longitudinal Placebo All had severe chronic spasticity One patient received an overdose due to human error.
study Patients followed and were refractory to oral drugs.
up after a mean of 3 mechanical failures, 6 wound complications, 22 catheter
19 months (5-41 complications out of the 75 implantations.
months).
Dressnandt et al., Prospective Mean of 61 months. N=27, of whom 20 had MS. Ashworth score: decreased in all 20 MS patients.
st
1995 longitudinal At end of 1 year, Ages 38-66 years.
27
Germany uncontrolled mean dose was 189 Average age of MS patients was Frequency of spasm score: decreased in all 20 MS patients.
ug/day. 52 years. (N.B., the primary outcome reported in this trial was the
All with severe paraspasticity or ability to withdraw intrathecal baclofen after prolonged
tetraspasticity. treatment. This was reported to be possible in 5 MS
patients).
Gianino et al., 1998 Prospective Mean dose at 12 N=25, of whom 15 had MS. 9 patients withdrew due to questionnaire fatigue.
USA longitudinal months 298 ug/day. All had intractable spasticity of
uncontrolled spinal origin. Ferrars and Powers QoL index: No change between
Most were paraparetic, 6 were baseline and 2 months. It was felt that this lack of change
quadriparetic, 1 hemiparetic and 1 was due to the emphasis of the QoL on nonphysical
monoparetic. aspects.
Mean age 39 years.
SIP improved from 29.7 ot 21.7 (p=0.8)
Physical subscore went from 38.5 to 31 (p=0.001).
Psychological subscore went from 20.8 to 13 (p=0.025).
Ashworth score: decrease from 3.8 to 1.5 (p value not

stated).
Frequency of spasm score: 2.6 to 0.5 (p=0.00001).

Lazorthes et al., Prospective Individual doses in N=18, of whom 6 had MS. Ashworth scale: 2-4 point improvement on all 6 patients.
1990 longitudinal MS patients ranged MS patients ages 40-56 years.
France uncontrolled from 100 250 All patients had severe, Modified Davis and Gray scale for evaluation of motor
ug/day. debilitating spasticity and were performance: 1/6 large improvement, 1/6 moderate
Mean followup unresponsive to oral treatment. improvement, 4/6 no improvement in function.
was 18 months
(range 4-43 Abolition of painful spasms in 5/6.
months).
Functional improvement was noted in 1 MS patient.
Functional improvement was greater in patients with
traumatic lesions as opposed to those with MS.
2 MS patients had serious complications (overdose,

meningitis).
Middel et al., 1997 Double-blind 75-150 ug/day. N=22, of whom 12 had MS. Fall in Ashworth, spasm and pain scores in treated
Netherlands RCT for 13 Placebo Aged 19-70 years. compared to placebo groups at 3 months. Effect sizes 0.2,
Cost analysis of weeks Baclofen N=12 1.4 and 0.94, p<0.05, <0.01, <0.05, respectively.
this study is followed by Placebo N=10 No significant differences in the change in SIP or HSCL
covered in the longitudinal All 22 received intrathecal scores.
paper by Postma et observational baclofen in the observational
al. study for 52 study. All patients had chronic Significant fall in Ashworth, spasm and pain score on
weeks. disabling spasticity and were not treatment at 3 (not for pain) and 12 months.
responding to oral medication.
Significant improvement in SIP, HSCL on treatment at 3 and
28
12 months.
Ochs and Tonn, Prospective Mean dose 199 N=70, of whom 59 had MS. 2 MS patients died during the study but this was thought to
1996 longitudinal ug/day at 1 year. Ages 35-69 years. be unrelated to their treatment.
Germany uncontrolled All patients suffered from spinal
Study duration up to lesions resulting in severe Reduction in muscle tone at on average 2 points below the
5 years. spasticity. initial baseline Ashworth score. This was sustained over 5
Mean Ashworth score 4.1. years in 12 patients.
“Spontaneous spasms reduced but less reliably than muscle

tone.”
At baseline, 54% (38/70) were bedridden. After 6 months

22 of the 38 could leave bed and use a wheelchair. Initially,
14 patients were wheelchair bound. After treatment 4 of
these were able to stand.
Subjective assessment: after 6 months 19/22 patients and

20/22 physicians rated the outcome as good or excellent.
Patterson et al., Prospective Initial mean dose N=21, of whom 15 had MS. 7 patients died but this was thought o be unrelated to the
1994 longitudinal 223 ug/day. Mean age 46 years (range 24-67) treatment.
UK uncontrolled Effective mean dose All patients had severe spasticity Complications in 9 patients led to the pump being removed.
485 ug/day. and were unresponsive to oral This included infections leading to meningitis in 5 patients.
Treatment duration treatment. Ashworth scale: Complete and sustained fall in score in
varied from 9 to 79 None was ambulant. 16/21 patients. In 4 other patients there was short term
months. benefit.
Frequency of spasm score: 18/21 patients showed a
complete absence of spasms. 15/15 MS patients showed a
complete absence of spasms.
Barthel index: no change in any patients, possibly due to
inappropriateness of this measure.
16/21 patients showed sustained improvements but the 2
patients who showed the greatest improvements in terms of
mobility and ability to drive did not have MS.
Penn and Kroin, Prospective Initially 12-200 later N=6, 3 with MS. 1 patient withdrew.
1985 longitudinal 12-400 ug/day for 7 All had severe rigidity in lower All patients showed an immediate and long lasting return
USA uncontrolled months. limbs (Ashworth score 4-5) and from an Ashworth score of 4-5 to 1 (normal tone).
5/6 had frequent spasms. Spasms were controlled in all patients and stretch reflexes
5/6 non mobile were reduced in half.
1/6 partially mobile. None of the patients had any of the central side effects
Average age of 36 years (range which they had with oral baclofen.
19-54 years) Functional improvement in ADL (?) reported.
Table reproduced with permission from the NCCHTA; From Beard S, Hunn A, Wight J. Treatments for spasticity and pain in multiple sclerosis: a systematic
review. [Review] [154 refs]. Health Technology Assessment (Winchester, England) 2003; 7(40):iii, ix.
29
Regarding the use of intrathecal baclofen pumps to control spasticity in MS patients, Beard et al. (18)
made the following conclusions:
 The studies indicate that patients with severe spasticity are likely to benefit from treatment with
intrathecal baclofen in terms of a reduction in spasticity, improved ability to sit in a wheelchair,
possibly of standing and improved nursing care.
 Patients with less severe disability may also benefit from improvements in care, with ability to
transfer and the likelihood of a considerable reduction in painful spasms .
 There is some evidence that bedridden patients with very severe forms of MS are unlikely to benefit
in terms of improved functionality or mobility but may benefit from generally improved care and
hygiene.
 In spite of the weaknesses of the study designs, one can conclude from the benefits seen in these
studies that intrathecal baclofen has a positive outcome for MS patients with severe spasticity.
Institute for Clinical Systems Improvement (ICSI), United States, September 2000
ICSI conducted a review of intrathecal baclofen for lower extremity spasticity associated with cerebral
palsy.
Intrathecal baclofen is typically considered for 2 particular groups of patients:

1. Patients with either spastic diplegia or spastic quadriplegia who are ambulatory (with or without
assistive devices) but who have inadequate leg strength and who use their spasticity to stand and
walk. The goal of treatment is to walk with less effort.
2. Nonambulatory patients with severe spasticity (upper and lower extremities). The goal of
treatment is to facilitate the care of these patients.
ICSI summarized the following studies examining the effects of intrathecal baclofen in patients with
cerebral palsy (Table 9).
30
Table 9: Studies examining intrathecal baclofen in children with cerebral palsy From ICSI.
Study Design Dose Patients Results
Dralle et al., 1989 Case series Continuous N=10 Reduced spasticity.
daily dose of Ages 3-10 years
25-700 ug
required. Dose
increases
required over
time.
Albright et al., 1991 Double-blind RCT 25, 50, or 100 N=17 Muscle tone assessed at 2, 4, 6, and 8 hours after
Placebo ug of baclofen Mean age 12.2 years injection; upper extremity function at 4 hours.
or placebo on
successive Mean muscle tone in lower extremity decreased within 2
days. hours of treatment and remained low for next 6 hours
(p=0.0001).
No change in muscle tone of the upper extremity.
3 dose levels produced a similar response in lower
extremity muscle tone; each dose significantly different
from placebo (p<0.05).
No neurological side effects with 25 ug dose.
With 50ug, 2 patients experienced lethargy, agitations
and disorientation that resolved without incident.
Albright et al., 1993 Observational ? N=37, of whom 33 spasticity related Muscle tone assessed at baseline and at 3, 6, 12, 24, and
o cerebral palsy. 36 months (for 37, 32, 30, 22, 13 and 6 patients
respectively.
Group 1 = moderately severe spastic Upper extremity function and activities of daily living
quadriparesis (n=25) and capable of assessed at baseline and at 6 months.
self-care. 22 patients were
ambulatory. Overall:
Mean lower extremity muscle tone decreased at 3, 6, 12
Group 2 = severe spastic and 24 months (p=0.001) with too few data at 36 months.
quadriparesis (n=12) and were
incapable of self-care and spasticity Mean upper extremity tone decreased at 6, 12, and 24
impeded care. months (p=0.008). Muscle tone related to baclofen dose
for both the upper (p=0.02) and lower (p=0.001)
extremities.
Group 1:
Lower extremity, but not upper extremity muscle tone
decreased (p=0.007).
Upper extremity timed tasks performed faster (p=0.04.
Activities of daily living improved (p=0.04).
31
Group 2:
Upper and lower extremity tone decreased (p=0.001).
No changes in activities if daily living.
Adverse Effects:
No adverse cerebral effects noted.
Temporary side effects observed in 5 patients.
5 patients required operation to correct catheter-related
problems.
8 pumps removed including 4 due to infection, 2 due to
recurrent CSF leaks, and 2 due to inadequate therapeutic
benefit.
Gerszten et al., Case series. ? N=48, all with spastic CP. At least 1 orthopedic procedure completed in 29 (60%) of
1998 Age range 5-43 years. patients before pump implanted.
Effect of IT baclofen At pump placement time, surgery planned in 28 (58%)
on the need for Followed for 2 years. patients.
orthopedic surgery. Surgery performed in 10/28 patients; remaining 18
patients judged to no longer require surgery.
Pump malfunction observed in 11 (23%) of patients.

Wiens, 1998 Case Series Oral baclofen N=17 Lower extremity spasticity decreased (p<0.001)at both 1
Retrospective was not Age range 5-17 years. and 3 months.
effective for
these patients. Upper extremity spasticity unchanged.
Improved mobility noted for 71%
Improved ability to perform activities of daily living
associated with hygiene was noted for 35%
Improved feeding for 29%.
Complications included CNS changes in 29%, pump

malfunction in 6%, catheter malfunction in 12% and CSF
leaks in 29%.
Van Schaeybroeck Case series. 11 patients N=6, 5 with CP Dose dependent response (Ashworth scale) seen
et al., 2000 tested for IT Age range 15-44 years old. following bolus doses of 25, 50, 75, and 100ug;
baclofen significantly different from placebo (p<0.0001), although
response. 8/11 Followup data for 2 years. there was a significant reduction in spasticity following
had positive placebo (p<0.009).
response, but 2
did not have During first 12 months, spasticity scores lower than at
sufficient baseline (p<0.001).
followup data
(for 2 years). Pain decreased and QoL reported to be improved by all
patients. Overall function scores unchanged.
5/6 patients discontinued oral antispasmodic drugs.
32
1 mechanical complication (disconnected catheter).
Gilmartin et al., Multicentre 12 site Bolus 50ug, 75 N=51 in Phase 1. 7 withdrew after Phase 1:
2000 study. ug or 100 ug. Ages 4-31.3 years, mean 10.3 years. 3 placebo responses
2 no responses to 50 ug dose
Phase 1 screening 1 meningitis
RCT of 50ug 1 adverse effect of treatment.
baclofen bolus
versus placebo Pumps implanted in 44 patients.
bolus. 7 withdrew from Phase 2:
2 infection in pump pocket
Spasticity assessed 2 family issues
at 0.5, 1, 2, 4, 6, and 1 to become pregnant
24 hours after 2 deaths unrelated to baclofen treatment.
treatment. If
spasticity decreased 38 patients (74.5%) responded positively to the 50 ug
and patient did not bolus dose. Of those, there was improvement in average
respond to the Ashworth score for lower extremities at 2, 4, 6, 8 hours
placebo injection, (p<0.001). This response was different from placebo
patient eligible for (p<0.001). Upper extremity spasticity reduced (p<0.001).
pump implantation.
If not, 75 ug and 100 The remainder of the 44 patients responded to a 75ug or
ug doses attempted. 100ug bolus.
Phase 2. Open Among the 44 patients who received a pump, lower

label, long term, extremity spasticity was decreased from baseline at 6
continuous infusion months (n=42), 12 months (n=40) and 39 months (n=7).
study. Spasticity
assessed at 2 Mean dose at start was 75 ug; at 39 months mean dose
weeks, monthly for 6 was 402.5 ug/day.
months and then at
3 month intervals. Adverse events reported in 42 of the initial 51 patients
(total of 205 adverse events). Most events were minor.
Following events occurred in >2% of the population:
Hypotonia (15.1%)
Seizure (9.3%)
Somnolence (8.8%)
Headache (6.8%)
Vomiting (6.8%)
Nausea/vomiting (4.4%)
Nausea (3.0%)
Device-related adverse effects included 39 procedure-

related events (7 pocket seroma, 5 pocket infection, 4
catheter dislodged, 3 CSF leak, 20 other) and 20 system
33
related events (2 catheter break, 2 catheter dislodged, 2
back pain at catheter site, 14 other).
Gerszten et al., Case series ? N=24, of whom 21 had spastic CP Ambulation rated by physicians and therapists as
1997 and 3 with spasticity secondary to improved in 9 patients, unchanged in 12 and worse in 3
spinal cord injury. patients.
Age range 9-30 years.
Patients and family members rated 20 as improved, 3 as
unchanged and 1 as worse.
3 patients had complications: 1 pump infection, 1

catheter disconnection (proximal revision of catheter) and
1 catheter complication (required 2 separate revisions).
From: Institute for Clinical Systems Improvement (ICSI). Dorsal rhizotomy and intrathecal baclofen for lower extremity spasticity associated with cerebral palsy. Bloomington,
MN: ICSI; 2000
34
ISCI concluded:
 Intrathecal baclofen has the advantage of utilizing a trial dose to determine if the baclofen is effective
and allowing the adjustment of the treatment dose, if needed.
 Studies of intrathecal baclofen have focused on spasticity and range of motion measures. There are
limited data on functional outcome measures and a lack of long-term followup.
Trent Institute for Health Services Research (UK), January 2000
The purpose of the review by Sampson et al. (3)was to identify and review the evidence base for the use
of intrathecal baclofen in the treatment of spasticity and to outline the potential cost implications of
providing the treatment for all patients who may benefit.
Inclusion criteria consisted of: Trials investigating patients with CP, MS, SCI, traumatic brain injury or
hypoxic brain injury; trials including more than 1 patient; average followup period of at least 6 months.
Outcomes of interest were: Function; quality of life; pain; subjective patient/caregiver report of
effectiveness; or health service use.
Type of Evidence Available

Ninety-four studies were identified of which 68 were excluded. Twenty-six original studies and 1 meta-
analysis met the criteria for inclusion in the review of effectiveness.
Studies were sorted according to origin of spasticity:

 Eight studies included patients with spasticity of spinal origin
 Six studies included patients with spasticity of cerebral origin
 Twelve studies either included patients with spasticity of cerebral origin and patients with spasticity
of spinal origin, or, it was not clear whether the origin of spasticity was spinal or cerebral in some
patients.
Quality of Evidence
Sampson et al. stated that most studies were before and after observational trials. One study was a RCT
for part of the trial; the randomized part lasted 13 weeks.
Many trials did not describe the methods that were used to measure the functional outcomes. For
example, some trials stated that post-treatment some patients were easier to care for but gave no
indication of how this had been assessed.
Some trials used validated outcome measures, but other trials used outcomes measures that had not
necessarily been demonstrated as being reliable and valid.
Many reports did not provide a statistical analysis.
Sampson et al. stated that although the Ashworth and spasm scores provide a useful way of monitoring
spasticity, these scores do not provide information about how spasticity affects patients’ QoL. In view of
this and the fact that the meta-analysis by Creedon et al. already summarized the data on Ashworth and
spasm cores, the subsequent descriptions of trials included in this review do not include further
descriptions of the effect of intrathecal baclofen on these measures.
35
Effects of Intrathecal Baclofen Infusion in Patients with Spasticity of Spinal Origin
 Eight studies that included only patients with spasticity known to be of spinal origin fulfilled the
inclusion criteria (N=160 patients, including 78 SCI and 65 MS).
 The meta-analysis suggested that intrathecal baclofen may be effective in reducing spasticity of spinal
origin in at least 92% of patients.
 In terms of quality of life and functional outcomes, the only RCT demonstrated no significant
difference between placebo and baclofen groups in quality of life/functional measures at 3 months
post-implantation.
 The largest case series of intrathecal baclofen in spinal spasticity used subjective outcome
measures and did not report the numbers of improved patients (Ordia et al. 1996).
 According to Sampson et al., the remainder of the studies were uncontrolled open followup
studies, mainly using subjective outcome measures and usually involving relatively small
numbers of patients.(3)
Effects of Intrathecal Baclofen Infusion in Patients with Spasticity of Cerebral Origin
 Six studies which included only patients with spasticity of cerebral origin fulfilled the inclusion
criteria (N=111 patients, including 63 with CP; the majority of the remaining patients had traumatic
or hypoxic brain injury).
 The meta-analysis suggested that intrathecal baclofen may be less effective in reducing spasticity in
patients with spasticity of cerebral origin than in patients with spasticity of spinal origin.
 In terms of quality of life and functional outcomes, Sampson et al. stated that the studies were based
on uncontrolled open followup studies mainly using subjective outcome measures and usually having
relatively small numbers of patients.
Effects of Intrathecal Baclofen on Different Outcome Measures
 Different outcome measures were used in different studies and were often subjective.
 Many studies did not provide denominator data (e.g., report that 2 patients had decreased pain, but not
say how many patients suffered from pain before treatment).
 Sampson et al. (3)summarized the outcomes related to mobility, activities of daily living, dependency
and the need for nursing care and other quality of life issues. Only studies where appropriate
denominator data were provided were included. The following terms were used in Tables 5-9 below:
Mixed adults Study included patients with spasticity of both cerebral and spinal origin.
Cerebral Study only included patients with spasticity of cerebral origin
Spinal mainly adults Study only included patients with spasticity of spinal origin, most of
whom were adults.
Table 10 shows that overall:

 50/76 (66%) of bedridden patients became able to sit in a wheelchair
 31/36 (86%) had improved ability to sit comfortably
 13/18 (72%) improved wheelchair mobility
 25/26 (96%) had improved ability to transfer
 4/36 (11%) of wheelchair bound patients became ambulatory (with aids)
 15/47 (32%) ambulatory patients improved their ability to walk and 4/47 (9%) had deterioration of
their ability to walk
 3/29 (10%) became able to drive
36
Table 10: Outcomes related to mobility From Sampson et al.(3)
Outcome Studies Patient Result
Condition
Bedridden patients becoming able Becker CP or ABI 8/12
to sit in wheelchair adults
Stewart-Wynne Mixed adults 6/6
Ochs Mixed adults 22/38
Zierski Mixed adults 14/20
Overall 50/76 (66%)
bedridden patients became
able to sit in a chair
Improved ability to sit comfortably Becker 6 MS patients ON a 0-5 scale, average 3
point improvement in ability to
sit
Mertens Spinal adults 15/15 improved ability to sit
comfortably
Patterson Mixed adults 16/21 improved ability to sit
comfortably
Overall 31/36 (86%) had
improved ability to sit
comfortably
Improved wheelchair mobility Becker CP or ABI 3/6
adults
Overall 13/18 (72%) improved
wheelchair mobility
Ability to transfer improved Becker Mixed adults 8/9 major improvement
Azouvi 12 adults with Average improvement from 3.5
thoracic/lower to 6. on a 1-7 scale
cervical lesions
Mertens Spinal adults 17/17 improved ability to
transfer
improved ability to transfer
Wheelchair bound patients Concalves CP or ABI 1⁄4 wheelchair bound developed
becoming ambulatory (with aids) adults “handicapped walking”
Ochs Mixed adults 1/27
Penn Mixed adults 2/5
developed “handicapped
walking”
Ambulatory patients improving Broseta Mixed adults 1/7
their capacity to ambulate
Azouvi Adults with 5/12 (including 2/12 who
lower became able to climb stairs)
cervical/thoracic
lesions
Penn Mixed adults 1 of 2 ambulatory patients lost
ability to walk
Gerszten CP or ABI mean 6/21 improved walking ability
age 18 including 4/7 who only walked
in therapy became able to walk
at home.
2/6 who only walked at home
37
became able to walk in the
community (note 3 patients
also had deterioration in
walking ability).
Overall 15/47 (32%)
ambulatory patients
improved their ability to walk
and 4/47 (9%) had
deterioration of their ability
to walk.
Patients becoming able to drive Parke Mixed adults 1/8
Patterson Mixed adults 2/21
Overall 3/29 (10%) became
able to drive.
Table 11 shows that overall 45/62 (73%) of patients had some improvement in Activities of Daily Living
(ADL) scores; these improvements were usually not observed in bedbound patients.
Table 11: Subjective assessments of activities of daily living (ADL) From Sampson et
al.(3)
Condition
Activities of daily living improved Albright CP or ABI mainly 19/25 self-caring patients
(subjective impression – no children 0/7 non self-caring patients
scoring systems used)
Gerszten CP or ABI mainly 20/24 (deteriorated in 2/24)
children
Stewart-Wynne Mixed adults 6/6
Overall 45/62 (73%)
showed some
improvement in
ADLscores. Improvements
in ADL scores were usually
not seen in bedbound
patients.

 83/90 (92%) patients had improved ease of nursing care
 19/23 (83%) of patients had improvements with skin integrity problems
Table 12: Outcomes related to dependency levels and nursing From Sampson et al.(3)
Condition
Place of residence Becker Mixed adults Of the 3 patients who were hospitalized prior to
intrathecal baclofen, 2 became able to live in the
community and 1 in a group home. Of 3 patients in
chronic care institutions prior to intrathecal baclofen,
2 were able to move to a group home and one moved
to hospital (due to comorbidities and progression of
38
MS).
Need for personal Nance Mixed adults 2/7 had decreased need for personal attendants.
attendant services
Ability to dress Ochs Mixed adults 8/12 patients who required major help in dressing
required only a little help in dressing 6 months after
intrathecal baclofen.
1/4 patients who required a little help became able to
dress without help.
Eating alone Ochs Mixed adults 2/9 who required help became able to eat alone.
Parke Mixed adults 5/7 who required help became able to eat alone.
Dependency level Stewart- Mixed adults 6 adults – no measurable change in dependency
Wynne levels.
Improved ease of Albright CP or ABI 6/7 nonself-caring patients
nursing care mainly
children
Becker CP or ABI 18/18
adults
Becker Mixed adults 8/9
Patterson Mixed adults 16/21
Lazorthes Mixed 18/18
mainly
adults
Mertens Spinal adults 17/17
Overall 83/90 (92%) had improved ease of nursing
care.
Skin integrity Becker Cerebral Of 11 chronic decubital ulcers, 5 healed and 5
adults improved.
Becker Mixed adults 6/9 improved skin condition.
Parke Mixed adults 3/3 with skin problems had resolution of problems.
Overall 19/23 (83%) of patients with skin integrity
problems showed improvements.

 59/66 (89%) patients with spasm related pain had relief or complete resolution
 27/33 (82%) had improved urinary function
Table 13: Outcomes related to quality of life (QoL) From Sampson et al.(3)
Condition
Pain Broseta Mixed adults 9/10 with pain became pain free
Lazorthes Mixed 14/16 resolution of painful spasms
Loubser Spinal injury 6/6 with musculoskeletal pain had complete
adults resolution.
Mertens Spinal adults 9/9 with spasm related pain became pain free
Sahuquillo Mixed adults 8/8 with spasm related pain had relief.
Zierski Mixed 13/17 with spasm related pain became pain free.
Overall 59/66(89%) of patients with spasm related
pain had relief or complete resolution.
Sleeping Becker Mixed adults On a 0-5 scale, sleep improved an average of 2.9
points, from 1.6 to 4.5
Penn Mixed adults 7/7 had improved sleep.
39
Sexual functioning Ordia Spinal adults 4/59 resumed sexual activity (all females)
Loubser Spinal injury 1/7 improved sexual functioning
adults
Social Patterson Mixed adults 2/21 improved social life
Penn Mixed adults 3/7 returned to work
Middel At 1 year, no change, no psychosocial dimensions of
Sickness Impact Profile (SIP) score
Ordia Spinal adults 2/59 became employed.
Loubser Spinal injury 3/7 became able to take vacations
adults
Urinary function Broseta Mixed adults 5/9 bladder function improved.
Parke Mixed adults 2/4 who were dependent became independent
Penn Mixed 4/4 who were incontinent between catheters became
adults continent between catheters.
Nanninga Spinal adults 4/4 who were incontinent between catheters became
continent between catheters.
3/3 patients with indwelling catheters became able to
self catheterize.
Concalves CP or ABI 2/2 with bladder dysfunction showed improvement.
adults
Sahuquillo Mixed adults Of 3 with indwelling catheters, 2 had minimization of
leaks and 1 became able to self catheterize.
4/4 with voluntary voiding had decreased nocturia.
Overall 27/33 (82%) had improved urinary
function.
Table 14 shows that overall, functional outcome results were variable between studies.
Table 14: Studies using a validated scoring system From Sampson et al.(3)
Studies Patient Condition Result
Azouvi Spinal adults Functional Improvement Measure. 7-point scale. Overall
improvement in motor but not cognitive domains. Minimum 2
point improvement in bathing, dressing lower body, transfers and
locomotion.
Gianino Spinal adults Ferrans and powers QoL index – no improvements
Sickness Impact Profile (SIP) (0-100 scale) improved from 29.7 to
21.7. Physical subscore improved from 38.5 to 31.0.
Psychological subscore improved from 20.8 to 13.0. Changes
were measured at 12 months in 16 patients and were statistically
significant (p<0.005).
Mertens Spinal adults Functional Disability Score – composite score measuring pain,
spasms, wheelchair use, transfers and washing/dressing each on
a 4-point scale decreased from 13.4 to 5.8 (p<0.0001) (n=17
patients).
Middel Spinal adults Hopkins Symptom Checklist and SIP – no difference between
placebo and intervention group at 3 months.
At 12 months physical subscore of SIP improved from 41.5 to
31.5. No change on psychosocial subscore.
Patterson Mixed adults 0/21 showed improvements in Barthel score.
40
Complications of Intrathecal Baclofen reported in the meta-analysis by Creedon et al.(13)
The studies that were included in the meta-analysis by Creedon et al.(13) also examined complications.
Studies that reported side effects, and in which the type of pump used was known, were summarized
(Table 15). Overall, the majority of complications associated with intrathecal baclofen infusion consisted
of local infections, catheter problems requiring surgery and pump removal due to complication.
Table 15: Complications associated with intrathecal baclofen infusion From Sampson et
al.(3)
Complication Pump (n=222)
Overdose 5 (2%)
Pump removal due to 16 (7%)
complication
Catheter problems 37 (17%)
requiring surgery
Local infection 9 (4%)
A summary of the effectiveness of intrathecal baclofen infusion by Sampson et al.(3) is as follows:

 Continuous intrathecal baclofen infusion produces a reduction in severe spasticity of spinal origin in
most patients. The effect on spasticity in patients with severe spasticity of cerebral origin is likely to
be less, but beneficial change was also seen in this group.
 The QoL evidence is generally poor (consisting almost entirely of small, open, uncontrolled followup
studies with subjective outcome measures and a failure to report results separately in different patient
groups). However, the quantity of the evidence is large and many studies show effects in some
patients.
 Decisions about whether or not to use intrathecal baclofen infusion need to be based on an
understanding of the likely benefits in patients with different levels of function:
o Patients with very severe spasticity who are bedbound and difficult to nurse are likely to
benefit from being able to sit out of bed. Nursing care is also likely to be easier. Such
patients are unlikely to have improvements in ADL.
o Patients who use wheelchairs but have great difficulty in being seated in the chair are
likely to benefit by being able to sit much more comfortably.
o Patients with a reasonable degree of remaining function may show some improvements in
their ability to perform important functions such as transfers, feeding, dressing or
wheelchair mobility. Most studies do not quantify the level of improvement so it is
difficult to judge from the literature how great that improvement may be. Failure to show
large improvements in functional measures such as the Sickness Impact Profile
(SIP)suggest that such improvements may be modest. It is unlikely that patients will
show dramatic improvements in function, although there are a few reports where this has
occurred. The vast majority of patients will still require help to perform many of their
activities. However, in severe disability even modest improvements in function may be
very important to patients.
 The evidence for using intrathecal baclofen infusion to improve walking ability is very limited. Up to
one-third of ambulatory patients may show some improvements in ambulation. Some patients may
find that the loss of tone makes walking more difficult.
 Significant pain related to spasms and problems with skin integrity strengthen the case for using
intrathecal baclofen infusion. In addition, this technology may also improve urinary function, but
41
patients may still need to self-catheterize.
Cochrane Review: Pharmacological Interventions for Spasticity Following SCI, 2003
The objective of the review by Taricco et al. (16) was to assess the effectiveness and safety of baclofen
and other drugs for the treatment of long-term spasticity in SCI patients as well as the effectiveness and
safety of different routes of administration of baclofen .
Databases searched included the Injuries Group Specialized register, the Cochrane Controlled Trials
Register, Medline, Embase and CINAHL up to 1998. Selection criteria consisted of all parallel and
crossover RCTs including spinal cord injury patients complaining of “severe spasticity”. Studies where
less than 50% of patients had a spinal cord injury were excluded.
Overall, 9 trials out of the 53 retrieved met the inclusion criteria. Fourteen studies are still being assessed
by the authors. Of the 9 studies, 2 focused on intrathecal baclofen.
These included a 1989 study by Penn et al. (20) that was previously reported in the assessment by Beard
et al. (18) and a 1992 study by Kravitz (22) that is a substudy of the Penn et al. study. Six patients with
an active pump already implanted were studied in order to evaluate the effect of baclofen infusion on
electromyographic activity.
Taricco et al.(16) concluded that:

 Overall, there is insufficient evidence to assist clinicians in a rational approach to antispasticity
treatment for SCI. Further research is urgently needed to improve the scientific basis of patient care.
 The current rationale that assumes that a “decision tree approach” exists calling for the use of
progressively more complex treatments whose sequence is guided by documented failures of previous
steps appears particularly weak. This is why nonresponders eventually become candidates for
intrathecal baclofen after previous failures with less invasive steps.
(16) et al. stated the following implications for research:

 This review clearly indicates that further research is urgently needed to assure that patients with SCI
receive evidence-based care.
 Further studies should include larger groups of patients and most importantly, use more clinically
relevant measures of treatment effects, including Activities of Daily Living (ADL) and QoL measures
administered at appropriate time intervals with respect to the realistic goals of patient recovery.
 The vast majority of currently available studies have too short a followup period to be able to
realistically assess clinically relevant end points dealing with functional recovery.
 More head-to-head comparison studies are required to get a full picture of the cost-benefits profile of
the interventions, especially if a “step by step” treatment strategy (from simpler to more complex
protocols according to individual’s clinical responses) has to be used.
Centre for Clinical Effectiveness (Australia) (March 2000)
Villanueva and Anderson .(23) reviewed the evidence for the use of intrathecal baclofen for hereditary
spastic paraplegia. A literature search was conducted (up to February 29, 2000). Overall, the authors
found one systematic review published in 1997 (Creedon et al.(13)) and no studies on this topic published
since 1997.
42
The systematic review by Creedon et al. examined the effectiveness of intrathecal baclofen on general
severe spasticity. Data from 27 studies (490 patients) was examined. The study designs were varied:
double blind placebo controlled RCTs (n=7); prospective open trials (n=17); combined designs (n=2);
retrospective case series (n=1). The average age of patients was 36-years. The primary endpoints were
changes in Ashworth and Penn scores, duration of followup and dose at last followup.
The following results from Creedon et al.(13) were reported:
 Mean Ashworth scores decreased form 3.9 to 1.6 (p<0.001)

 Mean Penn scores decreased from 3.5 to 0.7 (p<0.001)
 Cumulative success of 78.21% was reported
 Over 16 months, dose increased by an average of 250% from baseline
Summary of Health Technology Assessments of Intrathecal Baclofen
 Overall, HTAs suggest that intrathecal baclofen is an effective treatment for spasticity (Level 2 and
Level 3 evidence).
o This is supported by the 1997 meta-analysis by Creedon et al. .(13) who found
statistically significant changes in both the Ashworth score and the spasm score before
and after treatment in all patients, but particularly in patients with MS and SCI. The
results for patients with CP were not statistically significant but did show a trend towards
improvement. This may have been due to the low numbers of patients with CP included
in the meta-analysis.
o The meta-analysis (18)also showed that 92% of patients who had a pump installed were
still using the pump at 1 year of followup, which may indicate that the problems
experienced with the pump and catheter may be minor.
o The Trent Institute for Health Services Research (3) conducted a review of the
effectiveness of intrathecal baclofen in the management of patients with severe spasticity,
and building on the Creedon review went on to look at functional outcome measures
(with limitations). They found that intrathecal baclofen led to functional improvements
including improvements in the ability to sit up in bed or to sit more comfortably in a
wheelchair, improved nursing care and moderate improvements in activities of daily
living.
o The NHS R&D systematic review of treatments for spasticity in MS (last updated in
2000) by Beard et al.(18) reported on 15 trials (including 3 double blind trials that
compared intrathecal baclofen to placebo) (Table 15). All 15 studies showed an overall
positive outcome for patients treated with intrathecal baclofen. In studies that reported
the Ashworth scale, scores fell almost universally by 2-3 points, typically from 3-4 pre-
implantation to 1 upon treatment. Similarly, there was a near universal abolition of
spasms, which was reflected in spasm frequency scores.
o The NHS R&D review by Beard et al.(18) stated that there is a great need for more
research into the treatment for spasticity in MS, including the development of better
outcome measures which relate to functional ability and patients’ QoL.
Summary of Medical Advisory Secretariat Review of Intrathecal Baclofen for Spasticity
A literature search performed after the most recent health technology assessment (ASERNIP-S) identified
8 studies that met the inclusion criteria. These studies are discussed below (Table 16).
43
Table 16: Quality of evidence
Study Design Level of No. Eligible
Evidence Studies
Large RCT,* systematic reviews of RCT 1
Large RCT unpublished but reported to an international 1(g) †
scientific meeting
Small RCT 2
Small RCT unpublished but reported to an international 2(g)
scientific meeting
Non-RCT with contemporaneous controls 3a 3
Non-RCT with historical controls 3b
Non-RCT presented at international conference 3(g)
Surveillance (database or register) 4a
Case series (multisite) 4b
Case series (single site) 4c
Retrospective review, modeling 4d 4
Case series presented at international conference 4(g)
*RCT refers to randomized controlled trial
†g=grey literature
■ Zahavi et al. (24) evaluated the change in impairment, disability and health related functional status
after 5 years in patients (N=21) with severe spasticity associated with multiple sclerosis or spinal cord
injury, who received intrathecal baclofen (Level 3 Evidence). This study was a followup of a previous
study by Middel et al. (19)
Inclusion criteria consisted of:

Patients >18 years of age with chronic disabling spasticity of spinal origin inhibiting personal care,
sitting, lying and transfers, accompanied by pain and stiffness or disturbed sleep
Insufficient response to treatment with maximal doses of oral baclofen, dantrolene and tizanidine
Sufficient understanding of the consequences of treatment.
Exclusion criteria consisted of:

Pregnancy
Neurological symptoms of supraspinal origin
Allergy to baclofen
During a 4-year period (1991-1995), a programmable pump for injecting intrathecal baclofen was
implanted in 38 patients. Since more patients in the first study were followed up for 26 weeks than for 1
year, the authors decided “to compare current measurements with those taken at the start of the study and
at 26 weeks of followup as there were likely to be more data available.”(24)
Of the 38 patients originally included in the study, 21 were available for followup. Seventeen patients
were not included for the following reasons:
n=1 Pump removed due to an infection

n=3 Administration of intrathecal baclofen was discontinued for “various reasons”
n=9 Died from complications of the underlying spinal disease or other medical illnesses not related to
the spinal disorder
44
n=2 Refused to participate in the study
n=2 Lost to followup
The mean age (standard deviation) of the patients was 54.6 (12.5) years and 53% (11/21) had progressive
disease (MS in all cases). Among patients with non-progressive disease, 6 had spinal cord injury, 1 had
adrenalopathy, 1 had anterior spinal syndrome, 1 had radiation myelopathy, and 1 had spinal angioma.
The mean duration of treatment was 84.9 months.
Zahavi et al. summarized the results of the assessments of impairment (Ashworth scale and spasm score),
disability (EDSS, AL and ISS) and health outcome measures (SIP and HSCL) at baseline, 26 weeks after
baseline, and at the final evaluation.
For the final evaluation versus baseline values, there was significant improvement in the level of
impairment (Ashworth scale and spasm score, p<0.05) and a significant worsening in the level of
disability (EDSS, AI and ISS, p<0.05).
For the final evaluation versus 26 weeks after treatment values, there was a significant worsening in the
level of disability (EDSS and ISS, p<0.05) and in one dimension (psychosocial) of perceived health status
(SIP, p<0.05).
For the final evaluation versus baseline values, there is a discrepancy between significant improvement in
the level of impairment using the Ashworth and spasm scores and the significant worsening in the level of
disability. Similarly, for the final evaluation versus 26 weeks after treatment values, it is unclear as to
why there was a significant worsening in the level of disability and in the psychosocial dimension of the
perceived health status. The authors suggested that the following points may have played a role in these
discrepancies:
 Several patients, particularly those with MS had cerebral symptoms such as cognitive dysfunction
at followup. Cognitive abilities were also reduced in the elderly patients, who comprised a
significant proportion of the study group. Help from family members and caretakers was needed
and this may have influenced some results.
 The progressive nature of the disease may have affected the results of the perceived health status.
More than half of the patients were >50 years old which may explain why no change was
observed in the physical aspects of perceived health status. The psychosocial dimensions are not
only related to achieving adequate control of spasticity and spasm, but may also be related to
other factors and circumstances.
 Drug tolerance is a possible factor in patients with both progressive and nonprogressive disease.
Other factors affecting spasticity and spasms such as urinary tract infections, wounds, pressure sores,
other medical conditions, physical therapy, orthoses, drugs influencing spasticity or spasms, and whether
contractures were present were also evaluated as these could influence the measurements as well as the
dose of intrathecal baclofen. Zahavi et al. stated that none of these factors was considered to have a
significant effect on treatment outcomes (no data reported).
There were no significant differences between patients with MS versus a nonprogressive disorder at
baseline, 26 weeks and at final assessment (data not reported by authors) though sample size was not
large enough to test significant differences.
There was a borderline significant difference (p=0.05) in the mean or maximum intrathecal baclofen dose
between patients with MS or nonprogressive disease. It is likely that a larger sample size would have
allowed the significance level to be more appropriately assessed.
45
Limitations to the study by Zahavi et al. include:
 An attrition rate of 45% (only 21 of the original 38 patients could be evaluated). An intent to treat
analysis was not discussed.
 The current study and the original study had different investigators recording measurements.
 Several patients particularly those with MS had cerebral symptoms such as cognitive dysfunction at
followup. Cognitive abilities were also reduced in the elderly patients, who comprised a significant
proportion of the study group. Help from family members and caretakers was needed and this may
have influenced some results.
 The progressive nature of the disease may have affected the results of the perceived health status.
More than half of the patients were >50 years old which may explain why no change was observed in
the physical aspects of perceived health status. The psychosocial dimensions are not only related to
achieving adequate control of spasticity and spasm, but may also be related to other factors and
circumstances.
 Small sample size.
 In some patients care was taken not to abolish muscle tone completely on the premise that patients
may be able to use their extensor tone for transferring. Three patients could still make use of their
extensor tone in this way and the dose was therefore adjusted in these cases, leading to a lower dose
being given.
 Drug tolerance is a possible factor in patients with both progressive and non-progressive disease.
 The sample included a mix of patients who were quadriplegic and diplegic.
■ Plassat et al.(25) conducted a retrospective case series (N=40) to analyze the long- term safety and
efficacy of intrathecal baclofen (Level 4 evidence). Forty-one patients who were implanted between 1988
to 2001 were recruited into the study. All patients had severe and intractable spasticity (Ashworth score
>3) and were not relieved by maximal doses of oral medications, or experienced unacceptable side
effects. The origin of spasticity was as follows (Table 17):
Table 17. Origin of Spasticity

Spinal Origin n=33 Central Origin n=8
Traumatic n=17 Cerebral palsy n=3
MS n=6 Anoxia n=2
Hereditary n=4 Cerebrovascular n=3
Tumoural n=4
Infectious n=3
Reprinted by permission from Macmillan Publishers Ltd: Spinal Cord, copyright 2004; Plassat R, Perrouin VB, Menei P,
Menegalli D, Mathe JF, Richard I. Treatment of spasticity with intrathecal Baclofen administration: long-term follow-up, review
of 40 patients. Spinal Cord 2004; 42(12):686-693.
In total, 29 patients were clinically examined. Three patients had died. Seven patients were interviewed
by telephone. If they were unable to answer the questionnaire due to cognitive deficits, information was
obtained from relatives or caregivers. One patient was unable to answer the questionnaire or be clinically
examined. Plasset et al. defined the followup duration as the period of time between implantation and
assessment, pump withdrawal or death.
Procedure
All patients responded to the test dose injections before pump implantation. The average effective test
dose of baclofen was 100.5+84.34 ug per day for spinal diseases and 143.5+197.32 ug per day for
spasticity of cerebral origin. In all, 57.5% of the implanted pumps were programmable, 22.5% were
constant infusion pumps and 20% were manually operated.
46
Followup
Patients were followed for an average duration of 4 years after pump implantation. The average maximal
dose used was 476+260.5 ug per day.
During the first year, the required doses “increased by an average factor of 2.8”. From the second year
onwards, an increasing proportion of patients reached a stable dose with the proportion rising to include
86% of patients at the end of the 5th year.
Pump replacement was performed 1.4 times per patient due to a complication in two-thirds of cases.
The original Ashworth score before implantation was always >3 (no further data provided) and the
average score at the final assessment was 1.8+0.6 (n=27) (no p value provided).
Eighty-five percent of the patients would have undergone the procedure again if they had to make the
decision. In 85% of patients, the ambulation status was unchanged.
Pharmacological Complications
Common side effects occurred in 54% (20 patients). The most frequent were drowsiness, somnolence,
nausea and vomiting.
Twelve percent of patients experienced severe side effects; 80% of these were directly related to pump
refill procedures. They included:
n=2 Respiratory arrest due to accidental overinfusion after pump refill

n=1 Overinfusion (profound flaccidity, sedation and vomiting) due to manual pump malfunction
n=1 Mild respiratory depression after a morphine test because of baclofen tolerance.
n=1 Malignant hyperthermia with multivisceral failure and death a few hours after pump refill.
Device Complications
In total, 62.5% of the patients experienced an episode of malfunction, 90% of them required surgical
intervention, and 47.5% required more than 1 intervention. The total rate of device malfunctions was 0.2
per year (31 device malfunctions/153 years of treatment). Table 18 gives details of complications;
catheters were involved in 58% and pumps in 42% of cases. Pump complications were confined to
manual pumps, except in one case where the malfunction of a constant infusion pump was probably
caused by unusually warm outside temperature.
Table 18: Catheter and pump incidents.

Catheter n=18 Pump n=13
Disconnection n=4 Disconnection of reservoir n=2
Migration n=4 Porosity of membrane n=2
Kinks n=3 Subcutaneous collection n=5
Obstruction n=3 Unexplained n=4
Fibrosis n=3
Others n=1
Reprinted by permission from Macmillan Publishers Ltd: Spinal Cord, copyright 2004; Plassat R, Perrouin VB, Menei P,
Menegalli D, Mathe JF, Richard I. Treatment of spasticity with intrathecal Baclofen administration: long-term follow-up, review
of 40 patients. Spinal Cord 2004; 42(12):686-693
The pump was removed and intrathecal baclofen stopped in 7 patients (17.5% of cases). The cause was
sepsis in 3 cases, baclofen overinfusion in 1, intolerable side effects in 1 and lack of use of manual pumps
47
in 2 cases.
Limitations to the study by Passat et al. included:

 Retrospective case series design.
■ In the United States, Bjornson et al.(26) used a convenience sample of 30 patients for a pilot study to
examine the oral motor, communication and nutritional status of children with spasticity of cerebral
origin during intrathecal baclofen therapy (Level 3 evidence). One interviewer administered a structured
in-person interview tool, data from which were collapsed into 4 change categories: Communication and
speech, feeding and nutrition, oral motor function, and gastrointestinal function. Functional severity was
ranked with the Gross Motor Function Classification System (GMFCS).
The average time since implantation of the pump at the time of the study was 2.1 years (range 0.3 to 5.3
years). The average dose was 447 ug (range 91 to 1060 ug). The baseline lower extremity Ashworth
score was 2.5 (range 2.1 to 2.8). At the time of the study, all patients had responded well to intrathecal
baclofen in terms of reduced spasticity with an average change in lower extremity Ashworth score of 0.9
(range 0.7 to 1.1).
Communication and Speech

Of the 23 children capable of speech production, 10 reported improvements.
Feeding and Nutrition

The appetite question was applicable to 26 children in the study, with 10 reporting improvements in
appetite since starting intrathecal baclofen. The question was considered not applicable by the caregivers
of 4 children who were totally dependent on gastrostomy tubes for nutrition.
Oral Motor Function

Saliva control was applicable to 26 children, with 10 caregivers noting improvement and 8 noting a worse
status after intrathecal baclofen. Nineteen children were capable of cup drinking, with 12 improved after
intrathecal baclofen.
Gastrointestinal Function
Stool frequency was applicable to all children, and 14 reported a decrease in frequency after intrathecal
baclofen. Eight children had an increase in stool frequency. All 30 children or caregivers reported on
stool consistency, with harder stools in 11 children and softer stools in 7 children. From comments
reported in the questionnaire it appeared that the changes in frequency and consistency represented the
occurrence of constipation (infrequent, hard, difficult-to-pass bowel movements).
There were no consistent changes reported in feeding time, ability to orally feed, chewing, swallowing,
gagging, nutritional supplements or ability to handle liquids of different densities.
Limitations to the study by Bjornson et al. (26) included:

 Case series design pilot study.
 The variability in results may be partly attributable to variation in priorities about the importance of
these issues from one child and family to the next.
■ Dario et al. (2) examined 20 patients with chronic intractable spasticity who received an implantable
intrathecal baclofen pump. Spasticity was caused by MS in 14 patients and by spinal trauma in 6 patients.
Clinical efficacy of intrathecal baclofen was evaluated by using the Ashworth Scale, the Spasm
48
Frequency Scale (SFS), and the Functional Independence Measure (FIM). All parameters were assessed
before intrathecal therapy and every 6 months after pump implantation.
At last followup, (mean 24.7 months, range 12-46 months), the mean scores were as follows:
Ashworth score preoperative 4.3+0.6

postoperative 1.7+0.7, p<0.01
SFS preoperative 2.4+0.5

FIM preoperative 35.7+9.6

Eighteen patients (90%) stated that they would have their implants again, but 2 (10%) would not.
Limitations to Dario et al. (2) included:

 Small case series design.
■ Fitzgerald et al.(27) examined 52 spastic tetraparetic children within a continuous intrathecal baclofen
infusion programme (CIBI).
At entry to the study, 17 of the 52 implanted patients could walk short distances with a frame or
assistance, a further 7 could bear weight but not walk, while 28 had no use of upper or lower limbs. Most
children were totally wheelchair dependent. Approximately one third had mainstream cognition, the
remainder having various degrees of learning disability. Of the 52 implanted patients, 48 (92%) had CP
in association with premature birth. One patient was dystonic and the remaining 3 had suffered cerebral
insults through drowning, trauma and non-accidental injury. Their ages ranged from 2.5 to 17 years.
Adverse Events
The optimum dose ranged from 50 to 900 ug/day. No adverse events occurred during the refill
procedures. The most common problem was catheter migration or fracture.
Outcome
 In all 49 other cases, carers reported improvements in nursing care. All of these saw a reduction in
spasticity and an improved range of motion in unfixed joints. Of the 17 who were ambulant prior to
treatment, walking was improved in 9 cases. One previously nonambulant patient began to mobilize
with walking aids.
 Anecdotal observations:
o Improvements in speech, swallowing, drooling and upper limb function.
o Many children appeared to become more socially interactive.
o Weight gain.
o Increase in seizures in a small number of children, but the authors believed this to be
related to weight gain after CIBI and subsequent subtherapeutic concentrations of
anticonvulsants.
o 2 children with progressive scolioses saw deformities improved; but 2 further cases had
progression of deformities. The authors were unable to say whether baclofen had any
impact on the rate of progression of mobile deformities.
49
Fitzgerald et al. stated that a prospective multicentre RCT for both spastic tetraplegics and ambulant
children centred at the Queens Medical Centre in Nottingham received approval and is currently
underway.
Limitations to the study by Fitzgerald et al. (27) included:

 Case series design (Level 3 evidence).
■ Gooch et al.(28) performed retrospective chart reviews to examine the device and major nondevice-
related complications in a group of 100 consecutive patients who received 117 intrathecal baclofen pumps
for the management of severe spasticity.
Twenty-four patients (24%) had a total of 48 complications. Several patients had more than one
complication (5 patients had 2 complications, 6 had 3 complications, 1 had 4 complications, and 1 had 5
complications). The followup period after pump placement ranged from 6 months to 5.6 years.
The most frequent complication was catheter disconnection, i.e., a disconnection of the catheter at its
connection point to the pump. Catheter disconnection was more common in patients using pumps with
catheter access ports than in those who had pumps without ports. Ten disconnections occurred in the 62
pumps (16%) with catheter access ports. One disconnection occurred in the 55 pumps without catheter
access ports (2%), p=0.02.
Seven of the 50 pumps with 1-piece catheters had disconnections (14%). Four of the 67 pumps with 2-
piece catheters had disconnections (16%), p>0.05.
Catheter dislodgement from the intrathecal space was the second most common complication and
occurred in 10 cases (8% of pumps implanted). Eight of the dislodgements were in the 62 pumps with
catheter access ports (13%) and 2 were in the 55 pumps without (4%), p>0.05. Seven of the 50 pumps
with 1-piece catheters had dislodgements (14%) and 3 of the 61 pumps with 2-piece catheters had
dislodgements (4%), p=0.05.
Limitations to the study by Gooch et al. (28) included:

 Retrospective case series chart review (Level 4 evidence).
■ Staal et al.(29) retrospectively studied QoL, complication rates, and length of intrathecal baclofen
treatment as reported on surveys sent to 56 patients in a community-based rehabilitation centre outpatient
clinic (Level 4 evidence). Forty-nine patients responded; 30 adults and 19 pediatric patients. Thirty-six
patients (73%) had been using the pump for more than 1 year.
Patients had the following diagnoses: Brain injury (n=11), SCI (n=14), CP (n=22), MS (n=4). One
respondent had both CP and SCI and 2 had both brain injury and SCI.
Forty-three respondents (88%) stated they felt the quality of their lives had improved.
Nineteen patients cited complications with their pumps. These included “other” complications (n=11),
infection (n=5), catheter dislocation/breakage (n=5), and premature battery failure (n=2). Comments in
the “other” category included:
 Increased spasticity when baclofen was low near a refill date and when the pump was empty (n=4)
 Pump “flipped” (n=2)
 Vomiting/headache/weight loss (n=1)
50
 Itching before pump refill dates (n=2)
 Alarm did not sound near refill date (n=1)
 “Bad reaction the day of a refill that nearly caused convulsions” (n=1)
Despite the complications, 46/49 patients said they would recommend intrathecal baclofen to others.
Three patients did not respond to the question.
Limitations to the study by Staal et al.(29) included:

 Retrospective survey.
 Incorrect calculations.
Points of Uncertainty in the Studies of Intrathecal Baclofen for Spasticity

Include:
 Not consistently demonstrated in all studies that patients are refractory to all prior 1st line forms of
treatment. Some authors (e.g., Shakespeare et al.(30))pointed out there have been no direct head to
head comparisons of many first-line treatments.
 Unclear how long a patient can stay on intrathecal baclofen, especially considering that the dose
increases due to tolerance.
 Unclear how long intrathecal baclofen can delay contractures and future surgical procedures.
 Lack of quantitative, objective data to determine if nursing care/patient transportation/quality of
life/activities of daily living are improved.
 Lack of firm guidelines for treatment of different kinds of spasticity:
 MS versus CP versus SCI
 Lower verus upper versus combined upper and lower spasticity
 Lack of published direct head-to-head comparisons of intrathecal baclofen versus alternate
technology (except the 1995 Albright et al. (31) study comparing intrathecal baclofen to selective
dorsal rhizotomy) (See next section).
 Several reports show a reduction in spasticity with intrathecal baclofen treatment, but none explicitly
demonstrate quantitative objective improvements in range of motion in the upper limbs or signs of
improved functional skills in comparative trials.
Intrathecal Baclofen Versus Selective Dorsal Rhizotomy
In 1995, Albright et al.(31) conducted a retrospective observational study to compare intrathecal baclofen
(n=38) with selective dorsal rhizotomy (SDR) (n=38) on upper extremity spasticity (Ashworth scale) and
range of motion in children with CP.
Intrathecal baclofen was recommended for 2 groups of spasticity patients:

1. Functional patients who utilized their spasticity to stand or walk, and who might lose ambulation
if their spasticity was eliminated by SDR. The goal of treatment was to improve function.
2. Severely affected children with spastic quadriparesis whose upper extremity spasticity was as
severe as the lower extremity spasticity. The goal of treatment was to facilitate care.
SDR was recommended for children with:

1. Spastic diplegia, many of whom were ambulatory, with or without assistive devices. The goal of
treatment was to improve gait.
2. Severely affected children with spastic quadriparesis whose upper extremity spasticity was less
51
than it was in the lower extremities. The goal of treatment was to facilitate care.
The baclofen doses in the functional patients were titrated to reduce lower extremity spasticity without a
deterioration of gait and in the nonfunctional patients the doses were titrated so that lower extremity
spasticity was reduced to an extent such that it did not interfere with patient care. Intrathecal baclofen
doses were not altered according to upper extremity tone. Postoperatively, all patients were examined at
3, 6, and 12 months and yearly afterwards. Spasticity was assessed by a neurosurgeon and range of
motion was measured by an occupational therapist. Examiners were not blinded to the treatment.
Albright et al. (31) reviewed the charts of the first 38 patients with cerebral spasticity who had been
treated with intrathecal baclofen for at least 6 months, and matched them with 38 patients who had been
treated with SDR during the past 8 years. Patients were matched according to pretreatment upper
extremity muscle tone (Ashworth scale) and functional status (nonfunctional if they were incapable of
independent self-care, and as functional if they were capable of self-care; functional patients were further
categorized as ambulatory or nonambulatory) (Table 19).
Table 19: Mean (standard deviation) upper extremity Ashworth Scale score.
Mean upper extremity Baseline 6 Months 1 year P value
Ashworth scale (baseline to 1 year)
Intrathecal baclofen 2.07+0.82 1.84* 1.66* <0.001

SDR 2.03+0.74 1.78* 1.7?** <0.005
P=0.86
*Standard deviation not reported
*Second decimal place not reported.
From: Albright AL, Barry MJ, Fasick MP, Janosky J. Effects of continuous intrathecal baclofen infusion and selective posterior
rhizotomy on upper extremity spasticity. Pediatr Neurosurg 1995; 23:82-85.
In patients treated by SDR, there was a correlation between baseline upper extremity score and reduction
in tone (p<0.001). “Patients with a baseline score of 3 were more likely to have a 1 point reduction than
those with a baseline score of 2.” (Table 19)
In the SDR group, an average of 45.5% of the posterior rootlets were divided, (range 24.9% to 75%). The
percentage of posterior rootlets divided did not correlate significantly with the reduction in upper
extremity spasticity (p=0.117).
There was no significant difference in the reduction of spasticity between functional and nonfunctional
patients in either the intrathecal baclofen or SDR group (p values not reported).
There were no significant changes in range of motion in any upper extremity joint, either 6 or 12 months
after either intrathecal baclofen or SDR.
The families in both patient groups subjectively reported positive effects in hand function, activities of
daily living, speech and mobility.
Limitations to the study by Albright et al. (31) included:

 No a priori sample size estimate/justification.
 Patient groups that had different treatment goals.
 Inappropriate statistics. The Ashworth scale is a nominal scoring system 1-5. It is unclear why the
authors performed calculations for continuous data.
 Combinations of inter and intra-group statistics.
52
 Inconsistent reporting of data. Standard deviation only reported for baseline data.
 Subjective data on hand function, activities of daily living, speech and mobility.
 Patient groups were treated at different times.
Studies of SDR and Rates of Orthopedic Surgery in Patients with CP
■ Chicoine et al.(32) retrospectively analyzed 178 children with spastic CP who underwent SDR between
the ages of 2 and 19 years during 1987 to 1991. The patients’ disabilities included:
n=58 spastic quadriplegia (33%)

n=116 spastic diplegia (65%)
n=4 spastic hemiplegia (2%)
Patients received physical therapy for a minimum of 6 months postoperatively. Followup intervals after
SDR ranged from 24 to 70 months (mean 44 months).
Preoperative clinical assessments, postoperative followup visits and telephone discussions with parents
and health care providers were used to document orthopedic surgery performed before and after SDR.
Orthopedic operations were categorized as adductor releases, heel cord releases, iliopsoas releases,
hamstring releases, femoral osteotomies, ankle/foot osteotomies or “other” (e.g., peroneal muscle tendon
transfers and releases, iliotibial band releases, partial patella resections, quadriceps muscle releases, and
plantar fasciotomies).
Because the literature contains no historical control for the rate of orthopedic surgery in children with
spastic CP, Chicoine et al. divided the patients into 2 groups. Group 1 consisted of 54 patients who
underwent SDR between 2 and 4 years of age, and Group 2 consisted of 124 patients who underwent
SDR between 5 and 19 years of age. A comparison of these 2 groups was used to assess the effect of
early versus late SDR on the lifetime rates of orthopedic surgery.
Overall, at the time of last followup, 68 (38%) of 178 patients in the study had undergone at least one
orthopedic operation before and/or after SDR, with a rate of 22% in Group 1 and 45% in Group 2.
The overall orthopedic surgery rate was higher for Group 2 than Group 1 (p=0.037).
Limitations to the study by Chicoine et al. include:

 Retrospective case series study design.
 The average rate at which orthopedic operations are performed in children with spastic CP depends
on many variables including the distribution of CP types and the age of patients. Additional factors
complicating such analysis include disagreement among orthopedists as to the optimum age for
surgical intervention.
 In the Kaplan-Meier plots for Group 1 versus Group 2 for overall operative rates, the trend is for the 2
plots to merge together. This may reflect that some of the operations were typically performed at a
later age for Group 1 compared to Group 2. In addition, this may reflect some clinicians’ decisions to
postpone orthopedic surgery until the child’s outcome from SDR is ore clearly defined. Therefore,
the overall rates of orthopedic surgery may not be lower for Group 1, but merely postponed until later
in the life of the child.
53
Studies of Intrathecal Baclofen and Rates of Orthopedic Surgery in Patients with CP
■ Gerszten et al.(33) retrospectively reviewed the outcomes of 48 patients with spastic CP who were
treated with intrathecal baclofen in order to assess the need for orthopedic surgery of the lower
extremities in these patients.
The patients’ ages ranged from 5 to 43 years (mean 15 years). The mean followup was 53 months. The
diagnoses included 8 cases of spastic diplegia (16%) and 40 cases of spastic quadriplegia (84%). Patients
whose average lower extremity muscle tone decreased by 1 or more according to the Ashworth scale after
any intrathecal baclofen dose (50, 75, or 100 ug bolus injection) were considered to have a clinically
significant response and were offered implantation of a continuous infusion pump. The mean baclofen
dose was 306 ug/day (range 25-1350 ug/day).
After pump implantation , baclofen doses were increased during the first week until the mean lower
extremity muscle tone was perceptibly reduced and then increased again during the followup period
titrating the dose to the desired clinical response. Most patients received physical therapy 2-5 days per
week for the first 6 months postoperatively and 1-3 days per week for the next 6 to 18 months.
Documentation of orthopedic surgery performed before and after baclofen pump placement was obtained
from preoperative clinical assessments and postoperative followup visits.
Twenty-nine patients (60%) had undergone at least one orthopedic procedure before baclofen pump
placement. The mean patient age at the time of the first orthopedic procedure was 8 years old (range 2-19
years).
Subsequent surgery was planned at the time of pump placement in 28 patients (58%), however, 10
patients (36% of those in whom surgery was planned) eventually underwent orthopedic surgery after
intrathecal baclofen implantation. Further analysis of this group of 10 patients revealed that in all cases,
the surgical procedure was planned at the time of initial evaluation for intrathecal baclofen therapy. The
mean age for this group of patients was 10 years (range 5-19 years). Of the 10 operations, 8 were
performed within 12 months and 2 within 18 months of pump placement. No patient who underwent
surgery after intrathecal baclofen therapy required a second operation.
In the remaining 18 (64%) of 28 patients who did not subsequently undergo their planned surgery, the
same orthopedic surgeon believed that intervention was no longer required. This decision was based on
the degree of diminution of contractures such that joint range of m had improved and no significant
functional limitations were present.
The authors suggested that “Although improvement in spasticity does not result directly in improvement
of lower extremity contractures, dislocation or deformities, it may result in reduction of apparently fixed
contractures that in reality are dynamic contractures.”
Eleven patients (23%) required a revision of their pump for malfunction secondary to catheter-related
problems, including catheter fracture and catheter dislocation. Gerszten et al. stated that the initial thin
walled intrathecal catheter was redesigned and no further fracture occurred with the current thicker-
walled catheter.
Limitations to the study by Gerszten et al.(33) included:

 Retrospective case series design.
 No historical control group exists for the rate of surgery in patients with spastic CP.
54
 Given the wide range of ages, it cannot be determined if intrathecal baclofen therapy at an earlier age
has greater benefit over pump placement at a later age for a reduction in the development of lower
extremity orthopedic deformities that result from spasticity.
 The number of patients who avoided procedures that may require surgery in the future is not known.
 Lack of a control group undergoing physical therapy intervention.
Given the lack of high/moderate quality evidence for the use of intrathecal baclofen for spasticity, it was
decided that the previously mentioned alternatives for the treatment of spasticity would also be examined.
Cochrane Review: Antispasticity agents for Multiple Sclerosis (Shakespeare

et al.(30))
Shakespeare et al.(30) conducted a systematic review of the absolute and comparative efficacy and
tolerability of antispasticity agents for MS. A literature search identified articles up to June 2003.
Drugs included in the analysis were: baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin,
prazepam, threonine and cannabinoids. Intrathecal baclofen was not one of the drugs included in the
analysis.
All of the studies that were included in the systematic review by Beard et al (18)
were also included in the analysis by Shakespeare et al.
Main Results
 In total, 26 placebo controlled studies and 13 comparative studies met the selection criteria and were
included in this review.
 Fifteen of these studies used the Ashworth scale, of which only 3 of the 8 placebo-controlled trials
and none of the 7 comparative studies showed a statistically significant difference between test drugs.
 Spasms, other symptoms and overall impressions were only assessed using unvalidated scores, and
results of functional assessments were inconclusive.
Conclusion
 The variability of spasticity and the lack of a sensitive reliable, functional and symptomatically
relevant assessment tool for spasticity, contributed to the inconclusive results of placebo-controlled
trials attempting to document the efficacy of antispasticity agents currently in widespread use.
 Comparative studies have been similarly inconclusive.
 “No firm recommendations to change practice can be made from this systematic review and in
particular there is no good evidence to prefer newer over older agents.”
Shakespeare et al.(30) noted serious limitations to the studies:

 When considering the problem of spasticity, it is clear that both our understanding of the problem
and our ability to measure it are seriously deficient. This is reflected in the wide variety of
approaches taken to assess spasticity in the trials reviewed and the inconclusive objective results of
the vast majority of the trials.
 Difficulty remains in demonstrating the efficacy of the active drug against placebo.
 There remains a gap between published evidence and the daily experience of those who manage
spasticity. Better assessment tools are needed to confirm the clinical impression that the widely used
antispasticity drugs (baclofen, dantrolene, tizanidine) are more effective than placebo.
 The validity of the Ashworth scale -the only widely used assessment tool for spasticity- has been
seriously questioned and Shakespeare et al. were not aware of any validated method of assessing
55
spasm scores. Sixteen of the studies summarized reported an “Ashworth scale” but used different
methods to assess and score the Ashworth scale results, so a meta-analysis was not attempted.
 Only 3 of the 8 included placebo-controlled trials that reported Ashworth scale results showed a
statistically significant superior effect of active drug over placebo. None of the comparative studies
were able to show a statistical difference between the trial drugs.
 The concept of weakness reported by patients with spasticity is poorly characterized. Evidence for
differences between drugs was limited to limb power scores using unvalidated measures.(30)
 The decision to treat a patient with antispasticity medication is made for different reasons in
different patients:
o The immobile patient is treated for symptomatic relief and in order to make nursing care
and seating easier, whereas the ambulant patient is treated with the additional aim of
improving or preserving mobility.
o The diagnostic examination of the neurologist is not always an adequate predictor of the
functional examination of the physiotherapist or the daily experience of the patient.
o The currently available evidence does not help to answer the question of which agents
are best for treating different spasticity scenarios.
National Health Service Research and Development (NHS R&D), United

Kingdom, 2003: Treatments for Spasticity in MS
Beard et al. (18) conducted a systematic review of all treatments for spasticity in MS. Intrathecal
baclofen was previously discussed in detail, and below is a review of the alternative treatments
a) Phenol
Phenol injection into or around a nerve produces a temporary block that may last for months to control
muscle spasticity.
Beard et al. did not identify any controlled studies of the effect of phenol injection on spasticity, either in
MS or due to other causes. One controlled study was identified which compared the effect of 2 different
approaches to obtuator nerve block in patients with adductor spasticity, but this study was small and
appeared to use unvalidated outcome scales. Beard et al. stated that its greatest value may be as a case
series documenting the effect of obturator blockade, irrespective of approach used.
Four case series were identified which included patients with MS (although sometimes the number with
MS was not reported). Few details were given about the patients included in the studies, or how they
were selected, other than that they suffered from spasticity.
Summary of the direction of effect and impact on function:

 All of the case series reported relief of spasticity in a high proportion of cases.
Side effects
 Few side effects were reported in the case series.
 Complications reported included: “further muscle weakness”, sensory loss and genitourinary
dysfunction following subarachnoid block.
 Peripheral nerve blockade other than the obturator nerve is reported to result in “anesthetic skin” and
sometimes persistent severe pain.
 Arachnoiditis and sphincter dysfunction following intrathecal injection are also reported.
56
Summary
 The evidence of effectiveness of phenol blockade in treating spasticity was provided from case series
study designs. However, due to “the stable or deteriorating nature of spasticity and the prompt relief
observed in a high proportion of cases, it is reasonable to conclude that phenol injections do relieve
spasticity with a duration of action of some months.”
 There is insufficient evidence to draw conclusions about the functional impact of phenol for
spasticity.
b) Botulinum Toxin
Five Botulinum toxin (BT) papers met the inclusion criteria for the analysis. All patients in the selected
studies had chronic or severe spasticity and in many cases were nonambulant. Two studies recruited only
patients with MS.
Details of the included studies examining BT for spasticity are provided in Table 20.
Summary
 Although BT is not licensed in the UK for the treatment of spasticity in MS, there is evidence that it is
effective.
 Its role is restricted to those cases where the relief of spasticity is of greater functional benefit than
retaining any muscle strength.
 “In practice, this is likely to be the most severely disabled patients.”
57
Table 20: Studies examining the use of botulinum toxin for spasticity included in the NHS R&D review
Study Design Drugs and Patients Withdrawals Outcomes Results
Dose measured
Snow et al. Double-blind BT 160 ng (400 N=10 N=1 on Adapted Ashworth BT showed significant reduction in
(1990) placebo controlled units) i.m. in 3 Mean age 40 placebo scale. spasticity over placebo (p=0.009).
Canada crossover RCT muscle groups. years (23-61) Spasm Frequency Frequency score in BT group decreased
6 weeks All had stable MS. score from mean 2.9 to 2.7, not significant.
Nonambulant. Hygiene score Statistically significant improvement in
Recruited from BT group in hygiene score (p=0.009).
long stay No change in hygiene score for placebo
institutions. group. Greatest benefit found in most
severely affected patients.
No adverse effects noted.
Grazko et Double blind BT 25-250 units. Total N=20, of N=0 Modified Ashworth Reduction of at least 2 grades on the
al. (1995) placebo controlled Placebo whom 12 had Scale Ashworth score in all 5 patients with MS
USA crossover RCT Treatment 2 given spasticity and of lasting 1-3 months.
2 weeks after these 5 had MS.
treatment 1 or Ages 40-66 years “Subjective improvements in movement and
when any clinical Baseline posture”
effect had worn Ashworth score 3-
off. 4+
Cava (1995) Open trial. Patients BT. N=16, 10 of whom N=0 Modified Ashworth 13/16 patients (8/10 MS patients)showed
USA were followed up Intramuscular had MS (MS scale significant improvements. There was no
every 2 weeks, but dose per muscle patients who had Frequency of change in 3 patients (2/3 were MS patients).
the total duration of varied from 40 to taken spasm scale Mean Ashworth score changed from 2.6 to
the study is not 180 units. corticosteroids in Pain scale 1.3. This change was statistically significant
clear. Duration of Maximum dose previous 6 (P value?)
effect was found to range 270-300 months excluded) Spasm frequency also declined but it was
be 3-6 months. units. All >18 years not statistically significant.
All had There was a large reduction in pain
dysfunctional limb particularly in the MS patients (p value?).
spasticity but no Adverse effects were minimal, mainly
details of temporary bruising.
functional status.
Finsterer et Prospective, open BT mean N=9 N=0 Turn/amplitude All outcome measures were assessed on a
al. (1997) label uncontrolled intramuscular Mean age of MS analysis (EMG 5 point scale by the physician, not the
Austria longitudinal with does per patient patients =52 measure) patient. The duration of followup varied.
followup after 17-57 276 units. years. Activities of daily There is no evidence that this scoring
days after initial Mean dose per 5 had severe living. system has any validity.
injection. muscle 116 units. spasticity. Pain. All 5 MS patients showed an improvement
3 of the patients 3 had right upper Muscle tone in TAA, mostly by at least 2 points.
had a booster or lower limb (Ashworth scale) 4/5 MS patients showed an improvement of
dose owing to spasticity and 1 Range of motion. 1 point (Activities of daily living).
lack of response had 4/5 MS patients an improvement in pain.
58
initially, the tetraspasticity. 3/5 MS patients showed an improvement
number of The spasticity (Ashworth scale).
muscles treated was due to MS in MS patients showed an improvement in
was between one 5 cases. range of motion.
and five. Muscles Average duration Scores for all patients improved at a
were selected for of spasticity in MS statistically significant level.
injection if their cases was 16 Improvement did not appear to be dose
Turn/amplitude years. dependent.
analysis (TAA) Injection was tolerated by all patients
was >150. without complaint and there were no major
side effects.
Hyman et al. Double blind BT N=74. N=2 prior to Modified Ashworth Improved in all groups; no difference
(2000) placebo controlled 500 (n=21) All with probable week 4, N=14 score (muscle tone between groups although in placebo group,
UK dose ranging RCT 1000 (n=20) or definite MS prior to end of x spasm the improvement was due to a reduction in
1500 (n=17) units with disabling study at week frequency). spasm frequency only, with no reduction in
or placebo (n=16). spasticity of hip 12, due to Upper leg pain (4 tone.
Single treatment adductors, need for re- point scale). Proportion pain free increased in all groups,
(both legs only) Kurtzke treatment. Clinical global no difference between groups.
Expanded rating (4 point Median rating improved from severe to
Disability Status scale). moderate n all groups.
>7, stable for 6 Perineal hygiene Median score unchanged in placebo and
months, moderate score (6 point 500Unit groups; improved from 2 (one
pain, or difficulty scale). person able to clean/catheterise with effort)
in nursing, Time to re- to 1 (the same, with ease) in 1000-and 1500
hygiene score >2. treatment. Unit groups.
Mean duration of Primary analysis Median time to re-treatment 56, 99, 111,
MS 16-23 years. was performed on 119 days in placebo (n=7), 500-Unit (n=8),
Mean ages 47-54 the change from 1000-Unit (n=10), 1500-Unit (n=9) groups
years. baseline at week 4. respectively (p=0.015).
Concomitant Adverse events reported in 55% of patients
medication on active treatment, 63% on placebo.
continued.
59
c) Oral Drugs for Spasticity
Beard et al. (18) stated that there is limited evidence of the effectiveness of 4 oral drugs for spasticity
(baclofen, dantrolene, diazepam and tizanidine). “All appear to be approximately equally effective when
assessed clinically, though in no case is there any good evidence of functional benefit.”(18)
d) Non-Drug Therapies for Spasticity
Beard et al reviewed the following non-drug therapies that are used to treat spasticity in MS:
Neurotomy
 There is anecdotal evidence that selective neurotomy can be helpful in reducing spasticity only when
the spasticity affects just a single joint.
Myelotomy
 There is anecdotal evidence of a good success rate but the procedure is not reversible.
 Little or no evidence in patients with MS.
Chronic cerebellar stimulation (CCS)

 A review of CCS, which is used to reduce spasticity caused by CP, found that CCS resulted in an
85% reduction in spasticity. How the change in spasticity was measured was not reported.
Overall Conclusions of NHS R&D Review of General Treatments for Spasticity in MS

 Overall, there is limited evidence for the effectiveness of oral therapies for moderate spasticity.
 The findings of this review are supported by reviews of the same treatments for spasticity derived
from other etiologies.
o It is unclear whether or not the effectiveness of treatments for spasticity of etiologies
other than MS, such as SCI or stroke, can be compared.
o The evidence from other reviews suggests that the effectiveness of oral antispasticity
agents is very weak, despite their widespread use.
 “The evidence for intrathecal baclofen treatment is stronger. It is believed that the appropriate use of
intrathecal baclofen could result in significant savings in hospitalization costs in relation to bedbound
patients who are at risk of developing pressure sores.” To date, no formal economic analysis has been
conducted to provide evidence for this claim. (18)
 There is a need for more research into the clinical and cost-effectiveness of treatments for spasticity
in MS, including the development of better outcome measures which relate to functional ability and
patients’ QoL.
Systematic Reviews on the Use of Botulinum Toxin for Spasticity

Canadian Coordinating Office for Health Technology Assessment (CCOHTA), February
2005
BT inhibits the release of acetylcholine (a neurotransmitter) from the neuron, resulting in muscle
relaxation. It is injected directly into affected muscles. The dose generally depends on which muscle is
being injected. Repeat doses may be needed because the pharmacologic effect of BT usually lasts 2 to 4
months. BT differs from generalized pharmacotherapy (baclofen) and surgery (SDR) because individual
muscles can be directly targeted, depending on the goals of treatment.(34)
60
Garces et al. (34) conducted a systematic review of BT for upper and lower limb spasticity. The literature
review went up to April 2004.
BT is approved in Canada to treat spasticity in patients with CP and stoke.(34)
CCOHTA Results(34)
 Of the 33 RCTs included in the review, 12 focused on patients with stroke, 15 on patients with CP, 2
on patients with MS, and 4 on patients with other disorders.(34)
 Quality scores according to the Jadad scale varied (high=4 trials, moderate=16 trials, low=13 trials)
and the techniques used to prevent bias by concealing the allocation sequence were often unclear.
Despite the low scores of some trials, (5 single blind trials, 5 trials reported in an abstract), they
provided important clinical information.
BT for Upper Limb Spasticity in Patients Post-Stroke

 Nine trials compared BT to placebo.
 Patients receiving BT had decreased muscle tone and increased passive range of motion, but
statistically significant differences when compared to placebo were not shown in all studies.
 A meta-analysis of 2 trials examining the effect of BT on wrist muscle tone measured using the
Ashworth scale showed a statistically significant difference (weighted mean difference) (Table 21).
 One trial reported increased active range of motion.
 There were no statistically significant differences in adverse events (Table 22).
Table 21: Outcomes for stroke patients after BT treatment that were reported in a manner
appropriate for meta-analysis(34)
Outcome Measured Studies included Weighted Mean Heterogeneity
Difference (WMD) (p value)
and 95% CI
Effect of BT on muscle tone using Brashear et al. (n=64) -0.54 (-0.78, -0.30) P=0.005
Ashworth scale at wrist in patients Simpson et al. (n=9)
with stroke (fixed-effects model)
Effect of BT on muscle tone using Bakheit et al. (n=22) -6.28 (-16.02, 3.47) P=0.04
expanded Ashworth scale at Bakheit et al. (n=27)
elbow in patients with stroke
(random effect model)
Effect of BT on muscle tone using Bakheit et al. (n=22) -4.65 (-9.02, -0.28) P=0.04
elbow in patients with stroke
(fixed-effects model)
Effect of BT on muscle tone using Bakheit et al. (n=22) -11.73 (-16.72, -6.74) 0.51
expanded Ashworth scale at wrist Bakheit et al. (n=27)
in patients with stroke (fixed-
effects model)
Effect of BT on muscle tone using Bakheit et al. (n=22) -7.87 (-13.49, -2.24) 0.58
finger in patients with stroke
(fixed-effects model)
Effect of BT on passive range of Bakheit et al. (n=22) 2.58 (-6.37, 11.54) 0.16
motion at elbow in patients with Bakheit et al. (n=27)
stroke (fixed-effects model)
Effect of BT on passive range of Bakheit et al. (n=22) 9.00 (-0.28, 18.28) 0.78
motion at wrist in patients with Bakheit et al. (n=27)
stroke
Effect of BT no active range of Bakheit et al. (n=22) -4.29 (-13.83, 5.24) P=0.21
61
motion at elbow in patients with Bakheit et al. (n=27)
Effect of BT in active range of Bakheit et al. (n=22) 2.03 (-6.80, 10.86) P=0.49
motion at wrist in patients with Bakheit et al. (n=27)
From: Garces K, McCormick A, McGahan L SB. Botulinum toxin A for upper and lower limb spasticity: a systematic review. 51.
2005. Canadian Coordinating Office for Health Technology Assessment (CCOHTA).
Table 22: Meta-analysis of adverse events in patients with stroke who received BT Treatment(34)
Outcome Measured Studies Included and Risk Difference and Heterogeneity
Treatment (n/N) 95% CI (p value)
Adverse effects with BT treatment Bakheit et al. (25/63) -0.01 (-0.16, 0.13) P=0.98
in patients with stroke Bakheit et al. (3/20)
Bakheit et al. (20/32)
Patients with Stroke and Lower Limb Spasticity

 Three trials in total.
 One trial compared BT to phenol (Kirazli and On):
o Muscle tone was decreased compared to phenol (p<0.05)
o Injections of phenol were reported to be more painful than those of BT
 One trial compared BT to placebo (Pittock et al.):
o Muscle tone was decreased compared to placebo (at 4 weeks p=0.0002 to 0.0116)
o Passive and active range of motion was greater in patients receiving BT compared to
placebo, but it was not reported whether the difference was statistically significant
o Walking speed was not significantly different compared with placebo
o The overall rate of adverse effects was similar to placebo
 One trial compared BT, functional electrical stimulation and physiotherapy to physiotherapy alone
(Johnson):
o Walking speed was significantly faster with BT and physiotherapy compared with
physiotherapy alone (p=0.04).
Patients with CP and upper limb spasticity

 Two trials were identified.
 Neither trial reported the overall rate of adverse effects.
 One study showed statistically significant (p=0.04) improvement in the quality of upper extremity
skills test (QUEST, a standardized validated test of upper extremity function) (Fehlings et al.).
 One trial compared BT to placebo (Correy et al.):
o Muscle tone at the elbow and wrist was significantly decreased compared with placebo
for at least 2 weeks (p=0.01 and p=0.003 respectively)
o Active range of motion was significantly greater with BT treatment compared with
placebo at 2 weeks
 One trial compared BT and occupational therapy to occupational therapy alone (Fehlings et al.):
o There were no statistically significant differences in muscle tone in patients receiving BT
and occupational therapy compared to occupational therapy alone
Patients with CP and Lower Limb Spasticity

 Thirteen trials were identified.
 Eight trials compared BT to placebo:
o Three trials reported increases in passive range of motion but statistical significance was
inconsistent. Garces et al. stated that the reporting of data did not allow for meta-analysis
62
of this outcome
o Three trials measured significant differences in active range of motion (p<0.001 to
p<0.05)
o Gait as measured using video gait analysis (p=0.04) and a physician rating scale (p
=0.041 to 0.003) was significantly greater compared to placebo
o Other scales rated by patients, parents or physicians (physician rating scale,
questionnaires, Vulpe assessment battery and subjective functional assessment) generally
indicated an increased improvement in function compared to placebo (p<0.01 to <0.05)
o One trial designed to look specifically at pain, reported a significant difference compared
to placebo after adductor release surgery (p<0.02 to <0.001)
o When the incidence of adverse events from 3 trials was combined, patients receiving BT
experience significantly more adverse events than those receiving placebo. Common
adverse events were local pain and weakness (Table 23)
Table 23: Meta-analysis of adverse events in patients with CP who received BT treatment(34)
Outcome Measured Studies included and Risk Difference and Heterogeneity
Treatment (n/N) 95% CI (p value)
Adverse effects with BT treatment Baker et al. (48/94) 0.16 (0.07, 0.25) P=0.66
in patients with CP (fixed-effects Komanet al. (12/72)
model) Uhbi et al. (6/22)
 Two trials compared BT to casting:

o No significant difference in tone
o No significant differences in passive range of motion
 Two trials compared BT to physiotherapy
o One trial reported a significant (p<0.05) decrease in hip adductor and calf tone compared
to physiotherapy. However, the scores were only obtained from 8 of the 49 patients
o No significant differences in passive range of motion
 One trial compared BT to orthosis.
 There were no statistically significant differences in global motor function measure scores between
patients receiving BT and placebo, physiotherapy, orthosis or casting.
Patients with MS and Lower Limb Spasticity

 Two trials were identified
 One study reported a significant decrease in tone (p=0.008) (Snow et al.). Due to differences in the
reporting of muscle tone, the results of the trials could not be combined.
 Significant differences in passive and active range of motion, assessments of function and /or
disability and adverse events were not reported.
Patients with Various Diseases and Spasticity

 Four trials were identified.
 A wide range of results were reported and no overall conclusions could be made due to the diverse
patient population and treatment protocols.
CCOHTA Conclusion(34)
 BT resulted in decreased muscle tone across most trials and diseases.
 Increased range of motion, improved gait and improved function were shown in many studies, but
statistical significance was not always reached.
 Variability in results across studies may be due to the wide variety of disorders studied and the
63
differences in study designs and outcomes measures used.
o Combining results was seldom possible
 Adverse events reported in most studies are low in number and often temporary.
 Improved methods of reporting would lead to more robust conclusions about the comparative safety
of BT.
 Long-term patient-specific goal-focused outcomes are needed to further define the clinically
meaningful improvements in therapeutic outcomes.
Limitations to the CCOHTA Conclusions

 The dose, location and frequency of injection differ among trials based on patients’ requirements.
 Additional antispasticity drugs are used in some trials and not in others.
 Muscle tone and range of motion are commonly reported in trials but are not necessarily the most
important outcome:
o Reduction in muscle tone as measured by the Ashworth scale and improvement in joint
motion is often achieved, but whether these improvements translate into functional ability
is difficult to establish
o Reliability and validity of the Ashworth and modified Ashworth scale have been
explored, however, there is incomplete evidence that these scales reflect spasticity
o Lower scores on the modified Ashworth scale may not provide a valid measure of
spasticity (REF)
o These scales are ordinal and trial investigators may have used inappropriate statistical
tests (REF)
 Few goal-focused patient-specific outcomes (e.g., increasing the use of function of an upper
extremity, improving brace fit, preventing contracture, decreasing pain and increasing ease of care.):
o Goals are patient-specific, and each clinical case is unique such that each patient and
family may have different outcome priorities.
 Dose ranging trials have been conducted, but a dose-response relationship is not always evident. The
dose used is patient and muscle specific and may depend on such factors as the number of muscles to
be injected, severity of spasticity and the patient specific goal to be attained.
o An increased dose does not always lead to an increased incidence of adverse events in the
trials
 Weakness was reported as an adverse effect in some studies and may have been due to BT.
Weakness may also have contributed to reports of lack of coordination, abnormal gait, unsteadiness
or accidental injury.
 Trials are short-term ranging from 6 to 24 weeks. One trial lasted 12 months. Therefore, long-term
effects of repeated BT such as prevention of fixed contractures, prevention of surgical intervention,
and long-term improvement in gait or upper extremity function require further analysis.
 Most of the trials involve small numbers of patients and may be underpowered.
 Variability in outcome measures and missing data prevented the pooling of results:
o Muscle tone is reported using the Ashworth, modified Ashworth and the expanded
Ashworth scale
o Lack of meaningful data for meta-analysis. (i.e., mean difference from baseline and
standard deviation). Some trials used median and range or interquartile range. In most
cases, the results of 2-3 trials, sometimes by the same author, could be combined
o In the section describing the evidence of BT in patients with stroke and upper limb
spasticity, most outcomes could only be pooled from 2 trials.
64
Mulligan et al.(35) conducted a systematic review of the efficacy of BT in the treatment of spasticity in
ambulant children with CP. Inclusion criteria consisted of RCTs or self- controlled “experimental
studies”. Patients had to be:
 Children (age range 0-17 years)
 CP
 Ambulant and have lower limb disability affecting gait
Efficacy of intramuscular injection of BT was compared to no intervention, physiotherapy management

with and without casting/splinting, and the effect of placebo.
Outcome measures were:

1. Impairment measures of muscle spasticity, length and joint range of motion using the Modified
Ashworth Scale, the Modified Tardieu Scale and goniometry.
2. Functional measures of the GMFM and ambulation status
3. Gait analysis using subjective scales, 2-dimensional (video) analysis, 3-dimensional analysis and
electromyography
No literature search cut-off date was reported.
The search strategy produced 48 articles. A total of 16 studies met the inclusion criteria. Of these studies,
5 were RCTs and 11 were self-controlled trials. Of the RCTs, 2 compared BT to casting. Saline
injections as placebo were compared in the other 3 RCTs.
The review by Mulligan et al. was descriptive and for the results of the RCTs stated:
“While the calibre of these studies was deemed to be high or moderate, the results were not always
conclusive as to the efficacy of BT in functional outcome. Change in dorsiflexion through the gait cycle
showed the most consistent improvement with BT, with other measures such as gain analysis, other
functional measures and spasticity (when measured) did not consistently show significant improvement
when compared to casting or placebo.”(35)
Mulligan et al. concluded that “BT is effective in temporarily reducing spasticity and allowing a greater
range of movement at the ankle to enhance functional improvements in ambulant patients with CP
affecting their lower limb function.”(35)
Limitations to the study by Mulligan et al. included:

 Variability in reported outcome measures, injection location and concentration. “While there was
general consensus that BT has a positive effect on improving function, most of the studies reviewed
used multiple outcome measures to determine the effect of BT. This made comparison of article
outcomes difficult as each study used a variable mix of common outcomes to measure the effect of BT
on children with CP.”(35)
■ Boyd et al.(36) conducted a systematic review of the evidence for the use of BT in the management of
children with CP.
A literature search was conducted up to December 2000. Inclusion criteria consisted of:
 RCTs of management of the lower limbs using BT with placebo, control or comparison treatment
groups.
 Prospective non-RCT of BT in the lower limbs with objective outcome measures.
 Children with CP treated for movement disorders due to spasticity in the lower limbs.
 Intramuscular injection of BT irrespective of dose or muscle injected.
65
 BT treatments compared to normal saline, casts or physiotherapy through a randomized allocation
procedure.
The initial literature search identified 156 papers as having possible relevance to any management of the
lower limb in children with CP. Of these, 40 were excluded since they were retrospective or without
objective outcome measures. Ten RCTs met the inclusion criteria. Nine studies had concealed allocation
and 4 of the 10 had intent-to-treat analysis.
Five of the 10 trials used the physicians rating scale (PRS) as the primary outcome measure. The PRS
gives a composite score ranked from 0 (worst score) to 14 (best score). Success was defined a priori as a
2 grade or more increase in the score from the baseline composite score. The number of children in each
group who had a successful treatment with either BT or control with placebo injections or casting was
collated and the proportion of the total sample calculated.
The results of the treatment effect are reported as a standardized risk difference for all 6 studies using the
PRS after BT in the lower limb. All studies used the same standardized outcome measure with the
outcome assessed at 6-16 weeks followup and compared to baseline. The mean pooled risk difference for
BT and placebo studies was 0.25 (0.13, 0.37) and for BT and casting studies was 0.23 (-0.06, 0.53).
Twenty-five percent more of the BT treated groups would improve by 2 or more points on the PRS
compared to the placebo group (pooled sample size n=204). Similar results (although not statistically
significant) were observed for the BT groups compared to casting with a pooled risk difference of 0.23 (-
0.06 to 0.527) (pooled sample size n=38).
In some studies, different doses of BT were used.(36) The doses of BT in early studies were 2-4
U/kg/muscle. These doses are lower than what Boyd stated was current clinical practice which varies
from 7 to 11 U/kg/calf to a high of 9 to 13 /kg/calf or 25.5 U/kg/body weight for children with
diplegia.(36) It is unclear whether there is an optimal dose per muscle or per child for longest duration of
response and minimization of side effects.(36) When comparing clinical trials it is important to compare
dose of BT/kg/muscle, dilution of BT used, and type of BT and re-injection schedules.(36)
It is difficult to compare results of studies using different preparations of BT since some pharmacokinetic
studies suggested these have different properties.(37;38) Some studies suggested that 1 U BOTOX may
compare to between 3 and 5 U Dysport.(36)
There is no clear evidence of functional changes following BT as measured on gross motor function
measure (GMFM) in children treated with BT compared to control groups who received combinations of
physiotherapy with or without bracing or casting. There appears to be variability in functional change in
these studies according to patient severity, but it is difficult to compare studies reporting either goal scores
or total scores on GMFM.(36) The use of the GMFM as a sensitive measure of functional change may
create a dilemma for research, as the more mildly impaired children with hemiplegia and diplegia may be
the best responders to BT but may often reach a ceiling with the GMFM items.
In a group of children with severe functional impairment (Gross Motor Function Classification System
GMFCS Levels III to V), Boyd et al. reported a 6% change in total GMFM scores in both the BT with
brace treated and control groups over 12 months. There was a greater difference in goal scores between
the treatment and control groups but the difference was not significant. The amount of change in the
GMFM total scores over 12 months was greater in the mildly impaired children compared to the more
severely impaired children. Boyd et al. stated that these studies highlighted the potential for effect of
GMFM in children with severe diplegia or quadriplegia, or the lack of functional change in this group of
patients following BT.
66
Overall, Boyd summarized the current evidence for management of the lower limb in children with CP
using a grading system by Sackett.(36)
Grade A Evidence (extensive evaluation):

 Physiotherapy: Several RCTs with equivocal outcomes and a meta-analysis showing a small
treatment effect (Ottenbacher et al. 1987).
 SDR: Three large RCTs examined the efficacy of SDR compared to physiotherapy, and a meta-
analysis demonstrated the efficacy of SDR (McLaughlin et al., 2000).
Grade B
 Intrathecal baclofen: Two small randomized studies of short term baclofen infusion but no long-
term studies.
 Serial casting: Two small short term randomized trials.
Grade C (Prospective studies with objective outcome measures but no RCTs)

 Strengthening
 Orthoses
 Orthopedic surgery
Summary of BT for Treatment of Spasticity
 Level 2 Evidence of effectiveness

 Poor standardization and heterogeneity makes comparisons and summary difficult.
 To date, no-long term studies of outcome for use of BT in children with CP
o E.g., progression to surgery for ambulant patients and outcome of hip displacement in
children with adductor spasticity.
 Interrelationships of BT injections with orthoses, casting or surgery have not been examined in large
cohorts.
 There is a need for measurement of outcomes in terms of health related QoL and economic evaluation.
67
Systematic Reviews on Selective Dorsal Rhizotomy (SDR) for Treatment of
Spasticity
McLaughlin et al.(39) conducted a meta-analysis of 3 RCTs that examined children with spastic diplegia
who received either SDR plus physiotherapy (SDR + PT) or PT without SDR (PT only). Outcome
measures were spasticity (Ashworth scale) and function (Gross Motor Function Measure [GMGM]) up to
1 year after operation.
The literature search identified RCTs up to December 2000. Baseline and 9-12 month outcome data were
pooled (N=90 patients).
At baseline, 82 patients were under 8 years old and 65 had Gross Motor Classification System Level II or
III disability. Pooled Ashworth data analysis confirmed a reduction of spasticity with SDR+PT (mean
change score difference -1.2, p<0.001). Pooled GMFM data revealed greater functional improvement
with SDR +PT (difference in change score +4.0, p=0.008).
Multivariate analysis in the SDR+PT group revealed a direct relationship between percentage of dorsal
root tissue transected and functional improvement (p=0.0002).
McLaughlin et al.(39) concluded that SDR+PT is efficacious in reducing spasticity in children with
spastic diplegia compared to PT alone and has a small positive effect on motor function.
Limitations to the meta-analysis by McLaughlin et al.(39) included:

 Short-term results up to 1 year post surgery.
 Heterogeneity was not calculated or addressed by the authors. “In each of the 3 original studies, there
were not differences in baseline characteristics between treatment groups so the corresponding
analysis is not presented here for the pooled data.”
 No discussion of random or fixed effects models.
 No weighting of studies. Summary statistics were calculated using blocked Wilcoxon’s test and
ANOVA, including factors for treatment group, site and a treatment by site interaction.
68
Economic Analysis
Results of Literature Review on Economics of Intrathecal Baclofen Infusion
No formal economic analysis of intrathecal baclofen incorporating consideration of benefits was

identified from the literature, although a number of cost analyses were identified.
NHS R&D, United Kingdom, 2003
Beard et al.(18) conducted a literature search to identify economic evidence relating to treatments for
spasticity in MS. No formal cost-effectiveness analyses were found. Although literature was found on
treatment effectiveness, implying potential economic benefits through the improved management of
patients, none of these papers attempted to calculate formal cost-effectiveness ratios, estimates of utility
or overall treatment costs.(18)
Beard et al. identified 4 studies that closely approximated formal health economic evaluations and dealt
with the use of intrathecal baclofen in the treatment of MS related spasticity and its impact on
hospitalization rates. These 4 studies are summarized in Table 24.
Two of the studies are Canadian.(5;40). Nance et al.(5) compared the hospital admissions of 6 patients
with SCI or MS 2 years prior to intrathecal baclofen and 2 years post-treatment. Two years prior to
treatment, there were 376 inpatient hospital days (average 63 days). Two years after treatment, there
were 136 inpatient days (average 23 days), none of which were related to spasticity. The authors reported
an average net saving in 1995 of CDN $25,250 per patient, taking into account the cost of the pump and
hospital days. Nance et al. considered treatment to be cost-effective.
Becker et al.(40) examined the hospital costs of 9 patients 1 year prior and after implantation of an
intrathecal pump. Prior to implantation, patients had 755 acute hospital days (average 84 days). After 1
year of implantation, patients had 259 hospital days (average 29 days). Based on the cost of the hospital
stay of CDN $570 per day in 1995, reductions in hospital days gave an average saving of CDN $31,000
per patients (excluding the pump and implant).
The studies provided 3 separate estimates of bed days used for patients without or prior to intrathecal
baclofen: 19 days, 32 days, and 84 days. Beard et al. suggested that the differences may have been due
to differences in patient selection and care settings. Beard et al. assumed an average UK cost per
inpatient day of £211, which represents costs of £4,000, £6,800 and £17,700 respectively.
The number of bed days used during the year of implantation ranged from 21 days to 29 days.(18) This
corresponds to costs of £4,400-£6,100 for the hospitalization related to the intrathecal baclofen
procedure.(18)
Overall, Beard et al. stated that these studies imply the likelihood of significant cost offsets and patient
benefits from avoided hospitalizations post-treatment, but they did not attempt to combine this with any
form of cost of treatment and overall utility gain per patient.(18)
The cause of spasticity in these studies was not always MS. Causes included cerebral damage and SCI.
Therefore, generalization of the results specifically to MS patients may not be valid. The studies included
a very small number of patients.
69
Table 24: Economic studies of intrathecal baclofen From Beard et al.(18)
Study Patient Method Results Savings and Comments
Characteristics
Nance et al. (5) 6 patients Comparison of hospital 2 years prior to treatment: Average net savings of CDN $25,250 per patient, taking
1995 SCI or MS admissions, causally related to 376 inpatient hospital days (range 0-186 account of the cost of pump and hospital days (average
Canada spasticity, 2 years prior to days, average 63 days). cost per inpatient day CDN $813). Authors consider
treatment, 2 years post-treatment 2 years after treatment: treatment to be cost-effective.
136 in patient days (range 11-36 days,
average 23 days), none of which was due The number of days used within the post-treatment
to spasticity. years may be overestimated owing to use of placebo
All admissions post-treatment were related days in the screening phase.
to screening, implantation, treatment of
problems related to the intrathecal drug 2/6 patients reported ability to decrease personal
delivery devices and problems related to attendant services and 1 patient obtained employment
marked reduction in muscle tone. following treatment. 2/6 patients had skin ulcers which
healed following treatment. (unclear if these 2 patients
were the same 2/6 patients who reported ability to
decrease personal attendant services).
Postma et al.,(41) 18 patients Comparison of the number of Average number of hospital days in year of A calculation of the average direct costs that would be
1999 11 MS, 7 SCI days in hospital between groups implant in treated group was 31.5; 9.9 in likely to occur in a non-experimental situation was made
Netherlands 15 matched patients 1 year prior to implantation and 1 the test phase, 12.3 for the implantation in this study. For this analysis, only 2 days were
of similar age, sex year following implantation. phase and 8.4 resulting from allocated to the test phase, 10.3 days for the
and diagnosis (9 complications. implantation phase, and 8.4 days for complications. If
MS, 6 SCI) Average number of hospital days 18.7 for this had been the case, the average number of days for
the matched patients. the treated group would have been 20.7, i.e., 2
In the year following implantation, no additional days in comparison to the matched group.
significant difference was found.
For the non-experimental situation, the total average
cost of selection, testing, implantation and medical
followup amounted to US $28,473 per patient for the
first year.
Becker et al.(40), 9 patients. Hospitalization costs 1 year prior Prior to implantation: Based on cost of hospital stay of CDN $570 per day,
1995 6 MS, 2 cervical SCI and 1 year post-implantation 755 acute hospital days (range 0-319, reductions in hospital days give average saving of CDN
Canada and 1 head injury average 84 days). $31,000 per patient (excluding pump and implant).
Year of implantation:
259 days (range 10-48, average 29 days) At time of implantation, 6 of the 9 patients were
institutionalized in either chronic or acute care hospitals
owing to problems managing their spasticity. Following
treatment, 3 patients were discharged after prolonged
hospitalization, 2 to their own home and 1 to a group
home.
Savings likely to be underestimated as 2 patients were

in chronic care institutions prior to implantation and thus
would not have required acute care.
The authors concluded intrathecal baclofen to be

beneficial in terms of nursing assessment, patient
70
satisfaction and cost-effectiveness.
Ordia et al., 1996 10 patients Number of bed days used for 1 Prior to implantation: 95 bed days. Study does not report the proportion of days that are
USA MS or SCI year prior and 1 year following Post-implantation: 68 bed days, i.e., 2.7 related to spasticity and thus may include admissions
59 patients in total implantation. days per patient saved for general for unrelated causes. Similarly, there is no information
had pump implant, Hospitalizations were all cause hospitalizations in 1 year. as to the number of post implant bed days that are due
but only the first 10 and not specifically related to to complications from the procedure.
were included in the spasticity. Also 58 days used for screening and
cost study. implantation, i.e., 5.8 days used per patient The number of bed days reported is low as patients
for the screening and implantation. who received acute rehabilitation less than 1 year prior
to surgery were excluded from cost study.
Authors concluded that intrathecal baclofen is cost-

effective for treatment of severe intractable spinal
spasticity. This was based upon an average cost of US
$2,500 per day.
71
■ Sampson et al. (42) reviewed the effectiveness of continuous intrathecal baclofen infusion in terms of
improvements in function and QOL and considered the cost effectiveness of the intervention.
The full review of the evidence of effectiveness and cost assumptions was reported in the 2000 Trent
Institute for Health Services Research.(3)
Inclusion criteria were the same as previously reported, however, because the authors were also looking at
functional benefits, the studies had to allow calculation of the proportion of patients who achieved at least
one of the following outcomes:
1. Bedbound patients becoming able to sit in a wheelchair

2. Patients who had severe difficulty sitting in a wheelchair becoming able to sit comfortably
3. Wheelchair users improving their wheelchair mobility
4. Wheelchair users improving their ability to transfer
5. Wheelchair bound patients becoming ambulatory
6. Ambulatory patients improving their ability to walk
7. Improved ability to perform ADL
8. Improved nursing care
9. Patients with skin integrity problems who showed improvements in these symptoms
10. Reduction in spasm-related pain
Studies in which only measurements of patient impairment were recorded, such as the Ashworth score,
spasm score or reflex score were not included because these measures provide some indication of the
physiologic effect of the intervention, but do not necessarily relate to improvements in function or QoL.
Sampson et al. examined the impact of continuous intrathecal baclofen infusion on the HRQoL of 3
categories of patients with different levels of disability as follows:
Category 1, Bedbound patients experiencing severe spasm related pain

Category 2, Bedbound patients who were not in pain
Category 3, Wheelchair users with moderate spasm-related pain
The categories were chosen to represent a range of patients who may be considered for continuous
intrathecal baclofen infusion, “concentrating on the dimensions of mobility and pain, because these are
the most likely to be affected.”
Seventeen of the 94 studies identified met the inclusion criteria. Almost all the studies had open followup
with no control groups. In general, studies which used controls did so only to examine the effect of test
doses of baclofen rather than to assess long-term benefits. A variety of different outcomes were reported,
but functional and QOL outcomes were generally not measured using standard scores. Studies often
included patients with different causes of spasticity, thereby making it difficult to assess whether the
effectiveness of continuous intrathecal baclofen infusion was related to the underlying disease. In none of
the identified studies were QOL measures used, nor was cost-effectiveness considered.
In all the included trials, it was specified that patients must have severe disabling spasticity refractory to
treatment with oral medications and that they must have shown a response to the bolus dose.
Results of Studies
The studies indicated that approximately two thirds of patients who were bedbound because of their
spasticity could be seated in a wheelchair following intrathecal baclofen. Eleven percent of patients who
were wheelchair bound became able to walk with assistance. Forty percent of ambulatory patients had
some improvement in their ability to walk, however, a small proportion (9%) experienced a deterioration
in their ability to walk.(42)
Costs and Cost/Benefit of Continuous Intrathecal Baclofen Infusion - Sampson et al.(42), United
Kingdom
The cost of intrathecal baclofen infusion was estimated to be approximately £11,700 ($17,890 US) for the
assessment, test dose and implantation procedure with followup costs of £580 to £1,160 ($887-$1,174
US) per annum, based on an average of 4 to 8 refills per annum.
The total discounted cost over a 5-year period is estimated at 15,420 ($23,578 US). The costs per QALY
for Category 1, 2 and 3 were £6,900 ($10,550), £12,790 ($19,560), and £8,030 ($12,280) respectively.
Sensitivity Analysis
The initial cost of treatment was estimated at between £10,000 (using the lower cost estimates and
assuming a 2 day inpatient stay for the test dose and 5 days for the procedure) and £16,000 (using the
higher cost estimates and assuming a 5 day inpatient stay for the test dose and 8 days for the procedure).
Assuming an average of 6 refills per annum, this equates to a total discounted cost of between £13,000
and £19,000 for the 5-year period.
Sampson et al. stated that the cost effectiveness of continuous intrathecal baclofen infusion will rise above
£20,000 per QALY if the average annual QALY gain is less than approximately 0.15 or if the cost of
continuous intrathecal baclofen infusion is above £19,000 ($29,000 US) for the 5-year period.(42)
Conclusion
Sampson et al.(42) concluded:
1. There is sufficient evidence of an acceptable cost/benefit ratio to justify the use of continuous
intrathecal baclofen infusion in patients who have not responded to less invasive therapy and are
bedbound because of severe spasticity or who are wheelchair bound with severe spasm-related
pain.
2. The evidence for use of intrathecal baclofen in other patient groups is limited.
3. Future research should measure functional benefits in different patient groups and collect primary
HRQoL data ideally within the context of large, national trials.
Limitations to the study by Sampson et al.(42) included:
 Small number of trials in which functional rather than physiologic benefits of continuous intrathecal
baclofen infusion in severe spasticity were measured. However, no previous studies reviewed the
functional benefits from treatment or its effect on QoL. Although the cost was considered in some
previous studies, there were no previous attempts to value functional benefits in terms of HRQoL to
73
measure HTQoL directly, or to perform economic analyses. This is due partly to the paucity of
studies of functional benefits and partly to difficulties in choosing suitable outcome measures with
which to assess HRQoL directly in these patients.
 Estimation of cost/benefit ratio from pooled estimates of benefit in a series of small nonrandomized
studies by using assumed HRQoL states. Sampson et al. acknowledged that although this method is
imperfect, it is the best available option given the absence of primary HRQoL data and of large, high
quality trials in this area in which adequate followup and suitable functional outcome measures were
used.
 Results were concentrated on improvements in mobility and pain scores, which could be measured
using the EQ-5D. Improvements in other areas such as ambulation, ability to sleep, urinary function,
and social functioning may provide significant increases in the QoL for these patients, although
generic QoL measures such as the EQ-5D are not sufficiently sensitive to measure all these changes.
 The EQ-5D is based on valuations made by the general population, which may differ from those of
the treatment group.
 Direct costs of treatment were assessed. Potential savings that may accrue from reductions in
hospitalizations, orthopedic surgery or nursing care were not addressed.
Trent Institute for Health Services Research, United Kingdom, 2000
In addition to the above analysis published in 2002, Sampson et al.(42) (in the Trent Institute for Health
Services Research Report) also examined in detail:
 Reductions in hospital stay

 Pressure sores/decubitus ulcers
 Orthopedic surgery
 Reductions in oral treatments or other interventions
 Orthoses and other aids
 Reductions in caregiver resources
 Indirect costs
The costs of intrathecal baclofen arise from the cost of the procedure, followup and support, and costs of
potential complications.(3) The initial high cost of intrathecal baclofen therapy comes from screening,
the cost of the pump, and the hospitalization required to establish dose requirements.(3) Following initial
hospitalization, the costs are reduced considerably.(3) The pumps require a refill every 2-3 months.(3)
The cost of hospitalization reported within the literature varies depending upon whether complications
occurred. However, costs of complications should be less significant than those reported in many of the
studies due to improvements of the pump itself and physician experience.(3)
The typical length of stay in an acute care facility after an uncomplicated implant has been reported to be
between 3 and 10 days.(3) The average length of stay within an inpatient ward in the UKL is considered
to be around 5 days.(3)
Screening costs are incurred for all patients who are eligible for intrathecal baclofen, including those who
do not respond to the bolus dose. The test dose requires hospitalization of approximately 2 to 3 days.
Approximately 70% to 80% of children tested for response to intrathecal baclofen will undergo
implantation.
In more recent pumps, battery life may last up to 7 years.(3) Replacing a pump involves a procedure
similar to the initial implant.(3) Optimally, the pump is removed without affecting the catheter in which
74
case the procedure is less lengthy and requires less time in hospital.(3)
Sampson et al stated that whether the need for physiotherapy increases or decreases following intrathecal
baclofen infusion is unknown.(3) Albright suggested that the frequency of physical therapy after pump
insertion depends on the goal of the treatment; if the goal is to improve gait, therapy is often given 3 times
a week.(43) If the aim is to facilitate care, patients may need therapy once a week to maintain range of
motion, or not at all.(43)
In the UK, Sampson et al. estimated the cost of administering the test dose, pump implantation and
equipment to be between £10,500 and £12,900.(3) Additional annual costs of £580 to £870 were
estimated for followup and refill.(3)
The majority of complications usually occur within the first few months following implantation, with
further complications potentially arising from inappropriate dose. The potential for error depends upon
the experience of the surgeon, cognitive function of patients (related to patient selection) and the
caregivers.
Reductions in Hospital Stay
The impact on hospitalization requirements following intrathecal baclofen have been reported for the
United States (44), Canada(5;40) and the Netherlands(41). These are discussed below.
The savings reported by Nance et al.(5) and Becker et al.(40), both published in 1995, refer to
hospitalization days related to spasticity. Nance et al. reports a 40 day average reduction in the number of
bed days used over 2 years, and Becker et al reports a 55 day average reduction in the number of bed days
used over one year. The difference in numbers could be due to a greater degree of disability in the
population reported by Becker et al. as there were patients suffering skin breakdown who had
considerable resource requirements.
The savings reported by Ordia et al.(44) in 1996 do not relate specifically to spasticity and there is no
information provided as to the reason for hospitalization prior to or post intrathecal baclofen infusion.
Postma et al.(41) provided a detailed cost analysis of the costs and savings of intrathecal baclofen
infusion in the Netherlands. The study showed no significant difference in the number of hospital days
used by patients undergoing intrathecal baclofen infusion and the control group in the year following
intrathecal baclofen. For the implantation year, there were 18.7 days used on average by the control
group compared to an estimated average of 20.7 days related to the intrathecal baclofen procedure, and no
further days related to spasticity for the intrathecal baclofen group.
The 3 papers provide estimates of bed days used for patients without or prior to intrathecal baclofen:
19(41), 32 (63 days over 2 years)(5) and 84 days(40). The differences are due to different patient
selection and care settings. Assuming an average cost per inpatient day of £211, this represents costs of
£4,000, £6,000 and £17,000 respectively.(3)
The number of bed days used during the year of implantation ranges from 21to 29(41);Becker WJ, 1995
118 /id} days. This corresponds to costs of £4,400 to £6,100 for the hospitalization related to the
intrathecal baclofen procedure.(3)
Pressure Sores/Decubitus Ulcers
Pressure sores require either long periods of hospitalization or intensive community nursing care. It is
75
estimated that the total national cost in the UK for the treatment of pressure sores is approximately £755
million a year.(3) A full thickened sacral ulcer extends hospital stay by over 25 weeks at a cost of
£26,000 including extra staffing, drugs, dressings and hospital overheads. Costs for pressure ulcers differ
depending on the ulcer stage and care setting. Sampson et al. reported that local estimates of costs for
treating pressure sores are around £17,000 for a Grade 4 pressure sore and £5,000 for Grade 3.(3)
Orthopedic Surgery
The use of intrathecal baclofen in patients with spasticity due to CP may defer the onset of muscle
contractures, hip dislocations and potentially reduce the onset of scoliosis.(3)
The resulting reduction in the need for orthopedic surgery for patients undergoing intrathecal baclofen has
been reported by Gerszten et al.(33) and the authors suggested a reduction of 66% in orthopedic
operations needed following intrathecal baclofen. However, it is unclear whether the procedures were
avoided or delayed.(33) Neither the actual operations avoided, nor the costs associated with these
procedures, is documented within the article.
Local UK costing reports the costs of common orthopedic procedures for this CP patient group as
follows:
Adductor releases £2,000

Open or closed adductor tenotomy £1,500 to £2,000 (excluding to physiotherapy)
Hamstring release £2,500
Salter’s osteotomy or Chiari osteotomy £5,000
(for hip dislocation)
The number of orthopedic procedures avoided can depend upon the age of the child.(3) If the child is
treated within the early stages, it is considered likely that orthopedic procedures may be avoided
altogether.(3) In an older child (7-10 years), further orthopedic work, e.g., Achilles tendons and
hamstring releases may be necessary.(3)
Reductions in Oral Treatments or Other Interventions
No economic analyses are available that look at reductions in oral treatments post-pump implantation.
The cost of the drug for intrathecal baclofen should be offset by reductions in oral treatments, which are
prescribed in higher doses.(3)
Orthoses and Other Aids
No economic analyses are available that look at the use of orthoses and other aids post-pump
implantation.
Improved management of spasticity may lead to a reduction in seating aids, wheelchairs, spinal jackets
(due to scoliosis) and orthoses. A reduction in spasticity was reported to decrease the need for specially
designed wheelchairs designed to accommodate extended legs due to spasticity and allow a patient to
switch to a less expensive compact model.(45) A compact wheelchair would prevent the need for
remodeling of a home hallway and entranceways.
Reductions in Caregiver Resources
76
Although reductions in the caregiving time required and increased ease of care are frequently reported,
there is no quantification of the potential savings which may be realized.(3)
Similarly, savings have been reported in terms of reductions in the need for institutional care(40;41), but
the potential scale of the cost reduction is not quantified.
Indirect Costs
Further potential impact on costs may be achieved through indirect costs, as some patients were reported
to return to work following intrathecal baclofen, or to further their education due to reductions in
spasticity.(5;41) However, these costs have not been quantified within the literature.
Estimation of Cost-effectiveness and/or Cost-Utility
Sampson et al. stated that since there is no quantified measure by which the QALYs gained by the use of
intrathecal baclofen can be measured, it is not possible to provide an estimate of the cost per QALY for
the treatment. (3) However, by performing threshold sensitivity analyses, an indication of the potential
cost-effectiveness can be provided. (3)
Scenario 1: Using Average Costs per Year Over the Period of Treatment
Assuming total costs of £17,600 for 7 years of treatment, i.e. an average cost per year of £2,500
and a benefit of 0.13 QALYs per year (i.e., 0.88 QALYs for the 7-year period), would produce a
cost-effectiveness ratio of £20,000.
Assuming total costs of £15,800 for 5 years of treatment, i.e., an average cost per year of £3,200
and a benefit of 0.16 QALYs per year (i.e., 0.9 QALYs for the 7 year period) would produce a
cost-effectiveness ratio of £20,000.
Scenario 2: Discounting Costs and Benefits to Account for Different Costs in Each Year
Assuming a cost of £11,870 in year one and 870 in following years, and discounting both costs
and benefits at 6%, the number of QALYs gained over the 7 year period would be 0.83 to
produce a cost-effectiveness ration of £20,000, i.e., 0.14 QALYs for year one.
Assuming the pump lasts for 5 years and discounting costs and benefits at 6%, the number of
QALYs gained over the period would have go be 0.77 to produce a cost-effectiveness ratio of
£20,000, i.e., 0.17 QALYs in year 1.
Sensitivity of Cost per QALY Assumption to QALY Gains and Treatment Costs
Table 25 presents the number of QALYs that the treatment would need to provide per annum to achieve
different levels of cost-effectiveness, based upon variance in the initial cost of the treatment and
discounting costs and benefits at 6% per annum. As the cost of the pump and the inpatient stay for
implantation are the largest cost elements, variance in the initial cost will have the greatest effect upon
cost-effectiveness. The impact of altering the cost of refill/followup, depending upon the number of
refills per year, is significantly lower.
77
Table 25: Annual gains in health state values (QALY gains) required per year of
treatment for different cost-utility ratios and initial treatment costs - Costs and benefits
discounted at 6% per year over a 5-year period From Sampson et al.(3)
Initial Cost of Treatment
Cost per QALY ratio £10,000 £12,000 £14,000 £16,000
£5,000 0.58 0.67 0.76 0.85
£10,000 0.29 0.34 0.38 0.43
£15,000 0.19 0.22 0.25 0.28
£20,000 0.15 0.17 0.19 0.21
£25,000 0.12 0.13 0.15 0.17
The potential savings due to reduced resource requirements for the management of spasticity were
detailed by Sampson et al. (Table 26).(3)
Table 26: Summary table of potential savings From Sampson et al.(3)

Reduction Avoidance Potential
Savings
Hospitalization (MS & SCI) 20 days’ hospitalization £4,220
55 days’ hospitalization £11,605
Orthopedic surgery (CP) 1 adductor release £2,000
1 open or closed tenotomy £1,500
1 hamstring release £2,500
Hip dislocation £5,000
Pressure sore (MS & SCI) 50% chance of avoiding pressure sore – using cost of £13,000
pressure sore of £26,000
50% chance of avoiding pressure sore – using cost of £8,500
pressure sore of £17,000
Summary of Economic Analysis by Sampson et al.
 Cost of intrathecal baclofen is estimated to be approximately £11,700 for the initial assessment, test
procedure, implantation procedure and equipment. In addition, there will be further costs of around
£870 per annum for refill and followup.
 Battery life may be up to 7 years, although life expectancy may be less than this period for some
patients, notably MS patients.
 No studies report on QoL utilities for intrathecal baclofen.
 Assuming 5 years of benefit are obtained from the pump implantation, an average annual QoL utility
gain of around 0.16 would result in a cost-utility ratio of £20,000.
 Clinical opinion and Index of Health Related Quality of Life measures analysis suggested this scale of
QoL improvement to be possible.
 Although there is a lack of data in the literature, the high initial cost of intrathecal baclofen
implantation could be offset by reductions in pressure sores, other admissions related to spasticity,
orthopedic procedures and reductions in requirements for orthoses or other aids.
78
Cost Analysis of Intrathecal Baclofen Compared to Selective Functional Posterior Rhizotomy
(SFPR) – British Columbia (1995)
In 1995, Steinbok et al.(46) analyzed the relative cost of SFPR and continuous intrathecal baclofen in the
treatment of children with severe spastic quadriplegia related to CP at British Columbia’s Children’s
Hospital. No attempt was made to analyze the efficacy of the two treatments.
Nine children received intrathecal baclofen. All of these patients were severely affected, intellectually
delayed, spastic quadriplegic children who were mobilized in a special wheelchair pushed by an
attendant. Some of these patients were considered inappropriate candidates for SFPR.
Of a total of 100 children who had undergone SFPR from 1988 onward, 10 patients with the most severe
spastic quadriplegia related to CP were chosen to match the 9 patients in the baclofen group as closely as
possible with respect to the severity and extent of the spastic quadriplegia and intellectual delay. The
selected SFPR patients were all spastic quadriplegic, intellectually delayed and mobilized in a wheelchair
operated by an attendant, but were generally not as severely affected, particularly with respect to upper
limb function, as were the patients in the baclofen group.
The hospital records of these patients were reviewed and a clinical care flow chart was created to identify
the various points of contact with members of the health care team so that cost points could be identified
and costs calculated.
Since baclofen was provided free as part of a research protocol, and the real cost of the drug was not
known, the cost assigned for the baclofen was only the drug preparation fee charged by the pharmacy
department.
Costs were determined for a followup period of 1 year after the initial intervention for all health care that
was related to the SFPR procedure or to the continuous intrathecal baclofen therapy.
Initial baclofen screening consisted of insertion of a lumbar subarachnoid catheter attached to an

implanted access port and repeated injections of baclofen via the access port were carried out to determine
the efficacy of the drug. If the response to baclofen was satisfactory, the patient was readmitted to
surgery where the access device was removed and replaced with a continuous infusion pump.
Patients
The age range in the baclofen group was 6.0-17.5 years with a mean of 11.8 years. The age range in the
SFPR group was 6.0-16.1 years with a mean of 10.4 years. The patients in the baclofen group who had a
pump implanted were followed from 13 to 54 months (mean 36 months) and patients who received
rhizotomy were followed from 17 to 43 months (mean 27 months).
Of the 9 patients in the intrathecal baclofen group, 3 did not respond favourably to baclofen during
screening and did not have a pump inserted.
In the first postoperative year, 2 of the 6 patients with pumps required surgery for complications
associated with the baclofen treatment. One child had 4 further operations: 1 for effusion around the
pump; 1 for extrusion of the lumbar catheter from the subarachnoid space; and 2 for CSF fistula repair. In
the other child, 1 further procedure was performed for a pump effusion. In addition, 2 patients were
hospitalized for adjustment of the baclofen dose when there was deterioration in the relief of spasticity or
79
symptoms suggestive of overdose.
In the first postoperative year, no patient in the rhizotomy group was re-hospitalized for problems
associated with rhizotomy.
The total cost for the 6 successful implants was CDN $326,197.86. When one takes into account the cost
of CDN $58,780.71 incurred by the 3 patients who were screened but did not have a pump implanted, the
cost to the healthcare system per successful pump implant averaged CDN $64,163.10 in the first year
after implantation of the pump. The majority of the costs (72%) were related to hospitalization, which
occurred at a number of stages during the course of management.
All 10 patients underwent rhizotomy and the total cost for the 10 patients was CDN $169,135.40 with an
average cost per patient of CDN $16,913.54. Hospital costs accounted for 65% of the total costs.
Comparison of Baclofen and SFPR Costs
For both intrathecal baclofen and SFPR, the major costs incurred had to do with hospitalization. The
higher total average cost per patient treated with baclofen compared to SFPR was related to a more
prolonged hospital stay associated with preoperative assessment, screening for suitability for pump
insertion and management of complications. Paramedical costs were higher in the SFPR group because of
intensive postoperative physiotherapy.
Major limitations to the study by Steinbok et al. (46) included:

 Cost analysis was based on the experience at British Columbia’s Children’s Hospital starting from
1988 and therefore the results may not be current or generalizable to other institutions or to other
patient populations.
 Efficacy of the 2 treatments was not investigated.
 The two treatment arms were not comparable. The authors acknowledged that there were more
severely affected children in the baclofen arm.
 The number of children who received intrathecal baclofen was less than the number of patients who
had rhizotomies. The high incidence of complications with intrathecal baclofen may indicate a
learning curve, and that with more experience with intrathecal baclofen the complication rate may
decrease.
 Use of an implanted port to screen patients. Alternative ways to screen patients include a lumbar
puncture or externalized lumbar subarachnoid catheter.
 Intrathecal baclofen was experimental during the time of the study and was provided free to the
pharmacy. The authors stated that at the time of the publication, intrathecal baclofen cost CDN $136
per 10 mg vial.
 Part of the cost associated with both the use of intrathecal baclofen and selective rhizotomy was
related to experimental protocols and for both types of treatments, patient were in funded research
studies.
Ontario-Based Economic Analysis
Disclaimer: This economic analysis represents an estimate only, based on assumptions and
costing methodologies that have been explicitly stated. These estimates will change if different
assumptions and costing methodologies are applied for the purpose of developing implementation plans
for the technology.
80
Hospitalization Costs
In fiscal year (FY) 2003, 12 hospital separations were identified from the discharge abstracts database that
could have been associated with intrathecal baclofen pump insertion (a combination of ICD-10 CA
diagnosis codes and ICD-10 CA CCI procedure codes were used.) In fiscal year (FY) 2002, 7 hospital
separations were identified. Given the small number of cases, cases in both fiscal years were used to
determine the cost per case. The prospectively adjusted-for-complexity resource intensity weights (PAC-
10 weights) were used to determine a dollar value of each hospital separations based on a weight of 1.0
having a dollar value of $4,505 during FY 2003 and $4,539 in FY 2002 (Personal Communication, May
1
2005). The mean PAC-10 weight in FY 2003 was 1.97, and 1.80 in FY 2002, with an associated cost of
$8,113 per hospital separation in FY 2003 and $8,923 per hospital separation in FY 2002. The overall
average for both fiscal years was $8,625 per hospital separation with an average length of stay of 5.5
days.
There is also a short hospitalization involving a lumbar puncture (average 2.5 day length of stay) prior to
the insertion of the pump to determine suitability for pump insertion. Between 70% - 80% of patients
who undergo this procedure are eventually fitted with a pump (Personal Communication, May 10, 2005).
The PAC-10 weight for these hospital separations averages approximately 0.5, with an average length-of-
stay of 2.5 days. The associated cost is approximately $2,250 per hospital separation in which patients
are screened for suitability.
The total cost for hospitalizations is approximately $10,875, and based on the current volume of
approximately 10 procedures per year, the total provincial cost of hospitalizations related to intrathecal
pump insertion is approximately $108,750.
Device Costs
The cost of the pump is approximately $11,500 including the cost of refills for the first year (figure
provided by local Ontario hospital). As a result, the current annual device costs based on current volumes
of approximately 10 procedures per year would be in the range of $115,000. The pump generally lasts
from 5 – 7 years, at which point it must be replaced.
Professional (Ontario Health Insurance Program) Costs
Professional Costs per Treated Patient: (Source: MOHLTC Provider Services Branch)
$102 = pre-screening costs (includes 0.5 hour neurosurgeon time & outpatient clinic)
$55 = test dose (including lumbar puncture, lumbar catheter, procedure)
$936 = surgery for pump insertion
$204 = four refills per year performed by neurosurgeon
$1,300 = total OHIP costs per treated patient
1
One hospital separation with a PAC-10 weight  40 was removed from the sample upon which the average PAC-10
was calculated in FY 2002.
81
Total OHIP costs, based on a current volume of approximately 10 procedures per year, would be over
2
$13,000 annually.
Total Costs:
The total expected costs per treated patient in the first year are approximately $24,000, excluding the
costs associated with pathology, radiology, and microbiology. Based on approximately 10 procedures
per year, the total cost to the province of using this technology at current levels is approximately
$240,000 annually.
Downstream Cost Savings:
Based on reduced need for hospitalizations and medications for spasticity and its sequellae, we estimate
that the total savings to the system due to intrathecal baclofen pump insertion would be at least $5,000 per
case per year. Assuming remaining life expectancy of at least 30 years, the total cost savings to the
system could total $150,000 over a person’s lifetime or approximately $77,000, discounted to the present
at a 5% annual rate as suggested by the Canadian Coordinating Office on Health Technology Assessment
(CCOHTA.)
Diffusion:
Based on an estimated prevalence of spasticity appropriate for the pump of 1,500-2,400, there is a
potential backlog for procedures in this range. Based on the rate of pump insertion in the United States,
we estimate that if Ontario were to adopt similar utilization levels for this technology there would be
approximately 300 pump insertions per year at an annual cost of $8.2 -$8.4 million, until the backlog was
eliminated.
2
Since a greater number of people undergo the lumbar puncture than go through with the entire protocol
(approximately 20-30% more people), the total costs will exceed the per-patient treated costs by a factor of slightly
greater than 10--the current annual volume.
82
Existing Guidelines for Use of Technology
National Institute for Clinical Excellence (NICE), United Kingdom 2003
Multiple Sclerosis: Management of Multiple Sclerosis in Primary and Secondary Care
The following grading scheme was used by NICE (Table 27).
Table 27: Grading scheme used by NICE

Recommendation Evidence
Grade
A Directly based on category 1 evidence
B Directly based on:
 Category 2 evidence, or
 Extrapolated recommendation from category 1 evidence
C Directly based on:
 Extrapolated recommendation from category 1 or 2 evidence
D Directly based on:
 Extrapolated recommendation from category 1, 2, or 3 evidence
DS Evidence from diagnostic studies
HSC Health Service Circular 2002/2004
Evidence Source
Category
1a Evidence from meta-analysis of RCTs
1b Evidence from at least one RCT
2a Evidence from at least one controlled study without randomization
2b Evidence from at least one other type of quasiexperimental study
3 Evidence from nonexperimental descriptive studies, such as comparative
studies, correlation studies and case-control studies
4 Evidence from expert committee reports or opinions and/or clinical
experience of respected authorities
From: Multiple Sclerosis: Management of Multiple Sclerosis in Primary and Secondary Care; Clinical Guideline 8, November
2003; National Institute for Clinical Excellence
Spasticity and Spasms

 Each professional in contact with a person with MS who has any muscle weakness should consider
whether spasticity or spasms are a significant problem, or a contributing factor to the person’s current
clinical state. (GRADE D)
 If spasticity or spasms are present, then simple causative or aggravating factors such as pain and
infection should be sought and treated. (GRADE D)
 Every person with MS who has persistent spasticity and/or spasms should be seen by a
neurophysiotherapist to assess and advise on physical techniques, such as passive stretching and other
physical techniques to reduce spasticity and especially to avoid the development of contractures.
Families and carers should be taught how to prevent problem deterioration, and a monitoring system
should be put in place. (GRADE D)
 More active specific measures should be considered only if the spasms or spasticity are causing pain
or distress, or are limiting (further) the individual’s dependence and activities. In this case, both
benefits and risks should be considered carefully. A specific goal (or goals) should be set, but will
83
rarely include improved performance in activities. (GRADE D)
 Initial specific pharmacological treatment for bothersome regional or global spasticity or spasms
should be with baclofen or gabapentin. (GRADE A)
o The following should be given only if treatment with baclofen or gabapentin is
unsuccessful or side effects are intolerable:
 Tizanidine (GRADE A)
 Diazepam (GRADE D)
 Clonazepam (GRADE D)
 Dantrolene (GRADE D)
o Combinations of medicines and other medicines such as anticonvulsants should only be
used after seeking further specialist advice (GRADE D)
 People with MS who have troublesome spasticity and spasms unresponsive to simpler treatments,
should be seen by a team specializing in the assessment and management of spasticity. (GRADE D)
o The team should consider using one or more of the following:
 Standing and weight bearing through legs (GRADE D)
 Splints (GRADE D)
 Serial casting (GRADE C)
 Special or customized seating, such as tilt in space chairs (GRADE D)
 Intrathecal baclofen (GRADE A)
 Phenol injections to motor points or intrathecally (GRADE D)
 Intramuscular botulinum toxin should not be used routinely, but can be considered for relatively
localized hypertonia or spasticity that is not responding to other treatments. It should be used when
specific goals can be identified, (GRADE B) and:
o In the context of a specialist service that can consider all aspects of rehabilitation (e.g.,
seating) (GRADE B)
o By someone with appropriate experience and expertise (GRADE B)
o Followed by active input from a neurophysiotherapist (GRADE B)
Aetna, United States (November 30, 2004)
Implantable Infusion Pumps
Aetna considers implanted infusion pumps medically necessary durable medical equipment when all of
the following criteria are met:
 The drug is medically necessary for the treatment of members; and
 It is medically necessary that the drug be administered by an implanted infusion pump; and
 The infusion pump has been approved by the FDA for infusion of the particular drug that is to be
administered.
Anti-spasmodic drugs
Aetna considers an implantable infusion pump medically necessary when used to intrathecally
administer anti-spasmodic drugs (e.g., baclofen) to treat chronic intractable spasticity in persons who
have proven unresponsive to less invasive medical therapy as determined by the following criteria:
A. Member has failed a six-week trial of non-invasive methods of spasticity control, such as
oral anti-spasmodic drugs, either because these methods fail to adequately control the
spasticity or produce intolerable side effects; and
84
B. Member has a favorable response to a trial intrathecal dosage of the anti-spasmodic drug
prior to pump implantation.
Intrathecal baclofen (Lioresal) is considered medically necessary for the treatment of intractable
spasticity caused by spinal cord disease, spinal cord injury, or multiple sclerosis. Baclofen is
considered medically necessary for persons who require spasticity to sustain upright posture, balance
in locomotion, or increased function.
Documentation in the member's medical record should indicate that the member's spasticity was
unresponsive to other treatment methods and that the oral form of baclofen was ineffective in
controlling spasticity or that the member could not tolerate the oral form of the drug.
The medical record should document that the member showed a favorable response to the trial dosage
of the baclofen before subsequent dosages are considered medically necessary. An implanted pump
for continuous fusion is considered not medically necessary for members who do not respond to a
100 mcg intrathecal bolus.
Members must be monitored closely in a fully equipped and staffed environment during the screening
phase and dosage-titration period immediately following the implant.
Contraindications to implantable infusion pumps
Implantable infusion pumps are considered not medically necessary for persons with the following
contraindications to implantable infusion pumps:
1. Members with known allergy or hypersensitivity to the drug being used (e.g., oral
baclofen, morphine, etc.); or
2. Members who have an active infection that may increase the risk of the implantable
infusion pump; or
3. Members whose body size is insufficient to support the weight and bulk of the device; or
4. Members with other implanted programmable devices where the crosstalk between
devices may inadvertently change the prescription.
85
Blue Cross Blue Shield of North Carolina, United States, May 2003
Implantable Infusion Pumps
Implantable infusion pumps are considered eligible for coverage by prior authorization when used to
deliver drugs having FDA approval for this route of access and for the related indication.
Severe Spasticity
Implantable infusion pumps may be medically necessary for baclofen infusion in patients with severe
spasticity of spinal cord origin or cerebral origin in patients who are unresponsive to or who cannot
tolerate oral baclofen therapy.
Conclusion
• Level 2 evidence of the effectiveness of intrathecal baclofen infusion for the short-term reduction of
severe spasticity in patients who are unresponsive or cannot tolerate oral baclofen
• Level 3 evidence of the effectiveness of intrathecal baclofen for the long-term reduction of severe
spasticity in patients who are unresponsive or cannot tolerate oral baclofen
• Level 4 qualitative evidence of functional improvement for patients who are unresponsive or cannot
tolerate oral baclofen
• Intrathecal baclofen is cost-effective with costs which may or may not be avoided in the Ontario
health system
• True functional use remains to be determined
Appraisal/Policy Development
Policy Considerations/Implications
Patient Outcomes
Spasticity
Quality of life
Transfers
Bedridden patients sitting in wheelchair
Improved ability to sit comfortably
Improved wheelchair mobility
Decreased need for personal attendant services
Improved ease of nursing care
Skin integrity
86
Sleeping urinary function
Dosage Creep
 Creedon et al.(13) reported that it was in the immediate post-implantation period, that the most
accelerated dose increases occurred. Drug holidays are one method used to interrupt dose escalation,
but they may be temporarily successful.
 Longer-term followup is necessary to determine if these individuals ultimately require de-
implantation due to progressive drug tolerance or if the tolerance and dosing increases eventually
level off.
Demographics
Table 28: Estimated prevalence and incidence of SCI, CP and MS from the literature
Condition Incidence per Prevalence per
100,000 per year 100,000
SCI 1.7 72
CP 2.6 50
MS 3-7 100-200
Stakeholders
Less caregiving required by:

 Nursing staff in long term care facilities
 Families of affected patients
Physicians
 Neurosurgeons
 Anesthetists
 General surgeon
System pressures
Potential changes in:

Longterm care stay
Hospital stay
Patient transfer
Reduction in management of pressure sores
Reduction in pain
Orthopedic surgery
 Avoidance of adductor release, tenotomy, hamstring release and hip dislocation
Reduction in oral baclofen
Use of orthoses and other aids or adaptations
Care resources
 Improved sleep may lead to reductions in night care
 Improved ability to eat alone
 Patients may be seated and dress more easily
 Reduction in number of carers required to assist one person
87
Glossary
Baclofen: A drug designed to impede the release of excitatory neurotransmitters.
Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis
of the tissues supporting the muscles or the joints or from disorders of the muscle fibres.
Contracture deformity: Deformity of a limb without discernable primary changes of bone.
Diplegic: Paralysis affecting either both arms or both legs
Dorsal: Relating to the back.
Dorsal rhizotomy: A neurosurgical procedure designed to reduce spasticity in individuals with cerebral
palsy. The surgery requires testing individual sensory nerve rootlets to determine those rootlets that when
stimulated, produce abnormal electrophysiologic responses. Rootlets producing abnormal responses are
cut and normal responding rootlets are spared.
Hemiplegia: Paralysis affecting the limbs on only one side of the body.
Intrathecal: Injection of a substance through the theca of the spinal cord into the subarachnoid space.
Muscle release: Surgical technique that involves cutting tendons or muscle to increase muscle length.
Quadriplegia: Paralysis affecting all 4 limbs.
Serial Casting: Treatment consisting of a series of casts that are put on a part of the body to reduce
tightness and/or increase the amount of joint movement in patients who have trouble extending their arms
or legs. The limb is stretched, cast, and after 5-10 days, the cast is removed. The limb is then stretched
again and a new cast is applied. This continues until the joint is stretched as far as possible.
Spasticity: A motor disorder characterized by increased muscle tone with heightened deep tendon
reflexes.
Tendon release: Sectioning of tendon to treat contracture by lengthening the muscle-tendon unit.
Ventral: Located on or near the lower front of the body; the abdominal area.
88
Appendices
Appendix 1. Intrathecal Pump.
Used with permission from Medtronic, Inc.:

http://www.medtronic.com/servlet/ContentServer?pagename=Medtronic/Website/StageArticle&ConditionName=Chro
nic+Back+and/or+Leg+Pain&Stage=&Article=bpain_art_mdt_intra
89
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Ontario Health Technology Assessment Series 2005; Vol. 5, No.

Medical Advisory Secretariat

This report should be cited as follows:

How to Obtain Issues in the Ontario Health Technology Assessment Series

Print copies can be obtained by contacting MASinfo@moh.gov.on.ca.

Conflict of Interest Statement

The Medical Advisory Secretariat

ISSN 1915-7398 (Online)

About the Ontario Health Technology Assessment Series

Results of Literature Review for Intrathecal Baclofen for Spasticity 17

Summary of Medical Advisory Secretariat Review of Intrathecal Baclofen for Spasticity 43

To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of intrathecal baclofen

Advantages of intrathecal baclofen infusion are:

• True functional use remains to be determined

The estimated incidence of these conditions is shown below:

Spinal Cord Injury/Acquired Brain Injury

Clinical Scoring Systems to Assess Spasticity

Table 1: Ashworth Scale

Existing Treatments Other Than Technology Being Reviewed

Injections of Phenol or Botulinum Toxin

New Technology Being Reviewed

Advantages of intrathecal baclofen infusion are:

Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to proper

Results of Literature Review for Intrathecal Baclofen for Spasticity

Summary of Existing Health Technology Assessments

Foundation of Most International HTAs: Meta-analysis of Intrathecal Baclofen (Creedon

Overall results indicated that:

Summary of International Health Technology Assessments

Australian Safety and Efficacy Register of New Interventional Procedures-Surgical

A detailed summary of the 2003 ASERNIP-S report is provided below.

Study characteristics of these 2 case series are presented in Table 5.

Spasticity considered severe if Ashworth

Outcome measures and validity

Table 6: Safety results from case series in the assessment by ASERNIP-S

Efficacy results from the 2 case series are shown in Table 7.

Table 7: Efficacy results from the 2 case series studies

ASERNIP-S (17) concluded:

Beard et al.(18) addressed 2 general questions for NHS R&D:

Effect on Spasticity (Table 8)

One MS patient reported to be able to use staircase.

4 catheter dislocations, one catheter break, one catheter

# days in hospital: Average time spent in hospital reduced

A number of complications including: surgical catheter

Ashworth score: decrease from 3.8 to 1.5 (p value not

Frequency of spasm score: 2.6 to 0.5 (p=0.00001).

2 MS patients had serious complications (overdose,

“Spontaneous spasms reduced but less reliably than muscle

At baseline, 54% (38/70) were bedridden. After 6 months

Subjective assessment: after 6 months 19/22 patients and

Intrathecal baclofen is typically considered for 2 particular groups of patients:

Pump malfunction observed in 11 (23%) of patients.

Complications included CNS changes in 29%, pump

5/6 patients discontinued oral antispasmodic drugs.

Phase 2. Open Among the 44 patients who received a pump, lower

Device-related adverse effects included 39 procedure-

3 patients had complications: 1 pump infection, 1

Trent Institute for Health Services Research (UK), January 2000

Type of Evidence Available

Studies were sorted according to origin of spasticity:

Many reports did not provide a statistical analysis.

Effects of Intrathecal Baclofen Infusion in Patients with Spasticity of Cerebral Origin

Effects of Intrathecal Baclofen on Different Outcome Measures

Table 10 shows that overall:

Table 12 shows that overall: